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Online Library: Cancer
The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting cancer. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.
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Amino Acids and Cancer
Antitumor Effect of Lysine–Isopeptides
Source: Cancer Cell International 2002, 2:4
Affiliation: 1st Institute of Pathology and Experimental Cancer Research, Joint Research Organisation, Hungarian Academy of Sciences and Semmelweis University, H-1085. Budapest, Üllõi út 26, Hungary,1 Department of Organic Chemistry, Lóránt Eötvös University, H-1518. Budapest 112, P.O. Box 32, Hungary,2 Research Institute of Plant Protection, Hungarian Academy of Sciences, H-1022. Budapest, Herman O. ut 15., Hungary 3
Abstract: Isopeptides (ε-peptides) of lysine, with a given Mw and low polydispersity (10–400 units), were synthesized to study the relationship between their chemical structure and biological effect. The designed compounds were of high purity, low polydispersity and high stereochemical purity. The effect of the compounds was tested on a human erythroleukemia cell line (K-562) and on four transplantable mouse tumors (L1210 lymphoid leukemia, P38 macrophage derived tumor, Ehrlich ascites carcinoma, Lewis lung tumor /LLT/). The polymers of polymerisation degree 80–120 (Mw 10.2–15.4 KD) showed the strongest antiproliferative effect both on K562 cells and the tumors growing in vivo. This effect was manifest with a significantly higher survival rate as compared to the control (L1210, P38, Ehrlich ascites), furthermore, by a decrease in the number and size of liver and lung metastases (LLT).
Lysine-Specific Demethylase 1 Is Strongly Expressed in Poorly Differentiated Neuroblastoma: Implications for Therapy
Source: Cancer Res 2009; 69: 2065-2071
Affiliation: Department of Paediatric Oncology and Hematology, University Children's Hospital Essen;1 Institute of Cell Biology, University Hospital of Essen, Essen, Germany;2 Institute of Pathology, University of Bonn, Bonn, Germany;3 Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;4 Department of Pediatric Oncology and Hematology, Lund University Hospital, Lund, Sweden;5 Center for Clinical Research, Freiburg University Medical Center, Freiburg, Germany6
Abstract: Recently, several histone demethylases were identified catalyzing the removal of methyl groups from histone H3 lysine residues and thereby influencing gene expression. Neuroblastomas continue to remain a clinical challenge despite advances in multimodal therapy. This study addresses the functional significance of the chromatin-modifying enzyme lysine-specific demethylase 1 (LSD1) in neuroblastoma. LSD1 expression correlated with adverse outcome and was inversely correlated with differentiation in neuroblastic tumors. The study provides the first evidence that a histone demethylase, LSD1, is involved in maintaining the undifferentiated, malignant phenotype of neuroblastoma cells. The study shows that inhibition of LSD1 reprograms the transcriptome of neuroblastoma cells and inhibits neuroblastoma xenograft growth. The results suggest that targeting histone demethylases may provide a novel option for cancer therapy.
http://cancerres.aacrjournals.org/cgi/content/abstract/69/5/2065
Deregulation of Histone Lysine Methyltransferases Contributes to Oncogenic Transformation of Human Bronchoepithelial Cells
Source: Cancer Cell Int. 2008 Nov 3;8:15.
Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Abstract: To date, several histone lysine methyltransferases (HKMTs) have been identified and histone lysine methylation is now considered to be a critical regulator of transcription. However, still relatively little is known about the role of HKMTs in tumorigenesis. The study showed that differential HKMT expression in a lung cancer model in which normal human bronchial epithelial (NHBE) cells expressing telomerase, SV40 large T antigen, and Ras were immortal, formed colonies in soft agar, and expressed specific HKMTs for H3 lysine 9 and 27 residues but not for H3 lysine 4 residue. The results indicate the potential of these HKMTs in addition to the other targets for epigenetics such as DNMTs and HDACs to be interesting therapeutic targets.
Suppression of Proline-Directed Protein Kinase FA Expression Inhibits the Growth of Human Chronic Myeloid leukaemia Cells
Source: British Journal of Cancer (2000) 82, 1480–1484.
Affiliation: Department of Life Science, National Tsing Hua University, Hsinchu, 30013, Taiwan, Republic of China
Abstract: This study explored the potential role of PDPK FAin leukaemia cell growth by investigating the effects of partial inhibition of this kinase on the malignant phenotype of human chronic myeloid leukaemia cells (K562). Cloning of PDPK FAcDNA and its recombinant antisense expression vector and PDPK FA-specific antibody were successfully developed. The results demonstrate that specific antisense suppression of PDPK FAis sufficient to interfere with the growth of K562 cells, indicating that PDPK FAis essential for human chronic myeloid leukaemia cell growth. © 2000 Cancer Research Campaign
Arginine and Proline Alleles of the p53 Gene are Associated with Different Locations of Gastric Cancer
Source: Hepato-Gastroenterology, 2005, vol. 52, (No6), pp. 944-948,
Affiliation: Department of Surgery, China Medical University Hospital,1 Graduate Institute of Medicine, Chung-Shan Medical University, Taichung,2 Department of Pediatric and Medical Genetics, China Medical University Hospital,3 Department of Urology, China Medical University Hospital,4 Department of Life Sciences, Chung-Shan Medical University, Taichung,5 Taiwan, China
Abstract: This study of 51 patients and 59 control subjects evaluated the risk factors associated with p53 codon 72 polymorphism and gastric cancer carcinogenesis. The p53 gene codon 72 polymorphism was analyzed by polymerase chain reaction (PCR). The results of polymorphic genotype were stratified with the above risk factors and the associations were also examined. The proline allele at p53 codon 72 is associated with adenocarcinoma of the gastric cardia, and the arginine allele is associated with cancer of the antral and corpus locations. These findings suggest that different genotypes of the p53 gene in different locations of stomach might implicate a different cause of tumor growth.
Proline Oxidase Induces Apoptosis in Tumor Cells, and its Expression is Frequently Absent or Reduced in Renal Carcinoma
Source: J. Biol. Chem., March 14, 2003; Vol. 278, Issue 11, 9784-9789,
Affiliation: Texas A&M University System Health Science Center, Department of Pathology and Laboratory Medicine, College Station, Texas
Abstract: The study provides evidence implicating a role for proline oxidase in renal carcinoma that was observed in 8 of 12 primary renal cell carcinomas, with respect to their normal tissue counterparts. The study shows that a proline oxidase antisense vector repressed p53-induced up-regulation of proline oxidase, released of cytochrome c from mitochondria, and apoptosis in 786-0 renal carcinoma cells. Taken together, these findings support a role for proline oxidase as a downstream effector in p53-mediated apoptosis. The study hypothesizes that its altered expression can contribute to the development of renal carcinomas.
Cancer and green tea
Anti-carcinogenic effects of EGCG against estrogen-negative breast cancer cells
Epigallocatechin-3-Gallate Induces Apoptosis in Estrogen Receptor-Negative Human Breast Carcinoma Cells via Modulation in protein Expression of p53 and Bax and Caspase-3 Activation
Source: Mol Cancer Ther. 2005 Jan;4(1):81-90
Affiliation: Department of Dermatology, University of Alabama at Birmingham, 1670, University Boulevard, Volker Hall 557, P.O. Box 202, Birmingham, AL 35294, USA
Abstract: Using the MDA-MB-468 human breast cancer cell line as an in vitro model of ER-negative breast cancers, this study found that treatment of EGCG resulted in dose-dependent (5-80 microg/mL) and time-dependent (24-72 hours) inhibition of cellular proliferation (15-100%) and cell viability (3-78%) in MDA-MB-468 cells. Decrease in cell viability was associated with the induction of apoptosis (18-66%) which was analyzed by DNA ladder assay, fluorescence staining, and flow cytometry. The results of this study provide evidence that EGCG possesses anticarcinogenic effect against ER-negative breast cancer cells and thus provide the molecular basis for the future development of EGCG as a novel and pharmacologically safe chemopreventive agent for breast cancer prevention.
Anti-inflammatory mechanism of green tea polyphenols
Green Tea Polyphenols Block Endotoxin-Induced Tumor Necrosis Factor-Production and Lethality in a Murine Model
Source: J Nutr. 1998 Dec;128(12):2334-40.
Affiliation: Graduate Program in Nutritional Sciences, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA.
Abstract: This study analysis the role of green tea polyphenols in inflammations showing that tumor necrosis factor-alpha(TNFalpha) plays a pivotal role. The study postulates that green tea polyphenols regulate TNFalpha gene expression by modulating NF-KB activation through their antioxidant properties. In the macrophage cell line, RAW264.7, (-)epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNFalpha production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFalpha mRNA expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFalpha production in elicited mouse peritoneal macrophages. In male BALB/c mice, green tea polyphenols (given by oral gavage 2 h prior to an i.p. injection of 40 mg LPS/kg body wt) decreased LPS-induced TNFalpha production in serum in a dose-responsive fashion. The study concludes that the anti-inflammatory mechanism of green tea polyphenols is mediated at least in part through down-regulation of TNFalpha gene expression by blocking NF-KB activation.
Cellular and molecular effects of EGCG and green tea colon cancer
Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells.
Source: Clin Cancer Res. 2005 Apr 1;11(7):2735-46.
Affiliation: Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, New York, New York 10032-2704, USA.
Abstract: This study compared the cellular and molecular effects of EGCG with a well-standardized decaffeinated green tea catechin mixture Polyphenon E (Poly E) on human colon cancer cell lines. Both EGCG and Poly E preferentially inhibited growth of the Caco2, HCT116, HT29, SW480, and SW837 colon cancer cells when compared with the FHC normal human fetal colon cell line. The EGFR and HER2 proteins were overexpressed and constitutively activated in all of the colon cancer cell lines when compared with the FHC cell line. Treatment of HT29 cells with EGCG or Poly E caused an increase of cells in G1 and induced apoptosis. Both EGCG and Poly E caused a decrease in the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of the extracellular signal-regulated kinase and Akt proteins. The findings suggest that EGCG or Poly E may be useful in the chemoprevention and/or treatment of colon cancer. Poly E contains about 60% EGCG, yet pure EGCG and Poly E had similar potencies (expressed as microg/ml). Poly E may be preferable because it is easier to prepare and this mixture of catechins may exert synergistic effects.
Clinical and in vitro evidence of anti-cancer effects of green tea and EGCG
Green Tea and Cancer Chemoprevention
Source: Mutat Res. 1999 Jul 16;428(1-2):339-44
Affiliation: Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama 362-0806, Japan.
Abstract: This study demonstrates that epicatechin (EC) enhanced incorporation of 3H-EGCG into human lung cancer cell line PC-9 cells. EC along with another cancer preventive agent sulindac also synergistically enhanced apoptosis in PC-9 cells induced by epigallocatechin gallate (EGCG). A case-control study on breast cancer patients revealed that high daily consumption of green tea was associated with a lower recurrence rate among Stages I and II patients. All the results suggest that consumption of green tea is a practical and effective cancer preventive both before cancer onset and after cancer treatment.
EGCG and Breast Cancer – in vitro and in vivo effects
Green Tea Polyphenols and its Constituent Epigallocatechin Gallate Inhibits Proliferation of Human Breast Cancer Cells in Vitro and in Vivo
Source: Cancer Lett. 2007 Jan 8;245(1-2):232-41. Epub 2006, Mar 6
Affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Abstract: Several epidemiological studies have shown that breast cancer progression is delayed in the Asian population that consumes green tea on regular basis. This study reports the effectiveness of green tea polyphenols (GTP) and its constituent Epigallocatechin Gallate (EGCG) in tumor regression using both in-vitro cell culture models and in vivo athymic nude mice models of breast cancer. The results suggest that GTP and EGCG treatment inhibits proliferation and induce apoptosis of MDA-MB-231 cells in-vitro and in-vivo, and sustain contention that GTP and EGCG have anti-tumor properties.
Green Tea Polyphenol and Epigallocatechin Gallate Induce Apoptosis and Inhibit Invasion in Human Breast Cancer Cells.
Source: Cancer Biol Ther. 2007 Dec;6(12):1938-43.
Affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Abstract: This study have evaluated apoptotic and anti-invasive activity of green tea polyphenols (GTP) and its principal constituent Epigallocatechin gallate (EGCG) in MDA-MB-231 human breast cancer cell line. In in vitro human breast cancer model, EGCG and GTP induced apoptosis and significantly decreased invasion of breast cancer cells. Quantitative fluorescence labeling resulted in a 24-28% reduction in invasion through matrigel by EGCG and 15-23% reduction by GTP in a dose dependent manner. Focussed microarray analysis and reverse transcriptase polymerase chain reaction and zymogram analysis revealed inhibition of MMP-9 expression by polyphenol treatment. Furthermore, AKT was found to be inhibited both at the RNA and protein level by polyphenol treatment. Moreover EGCG and GTP decreased AKT phosphorylation as found out by Western blotting for Phospho-AKT (Ser-473). beta-catenin level was found to be decreased both in cytoplasm and nucleus. For the first time the study reports the connection of beta-catenin and AKT modulation by GTP and EGCG as a possible mechanism for the induction of apoptosis in human breast cancer cells and also inhibition in their invasive capacity.
EGCG effects on VEGF production in various cancer cell lines
Epigallocatechin-3-Gallate Decreases VEGF Production in Head and Neck and Breast Carcinoma Cells by Inhibiting EGFR-Related Pathways of Signal Transduction
Source: J Exp Ther Oncol. 2002 Nov-Dec;2(6):350-9.
Affiliation: Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, HHSC-1509, 701 W. 168th Street, New York, NY 10032, USA.
Abstract: This study found that epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, inhibited activation of the epidermal growth factor receptor (EGFR) and related signaling pathways in head and neck squamous cell carcinoma (HNSCC) cells. Treatment with EGCG inhibited the constitutive activation of the EGFR, Stat3, and Akt in both cell lines. These changes were associated with inhibition of VEGF promoter activity and cellular production of VEGF. The obtained results suggest that EGCG inhibits VEGF production by inhibiting both the constitutive activation of Stat3 and NF-kappa B, but not extracellular-signal-regulated kinase (ERK) or Akt, in these cells. Therefore, EGCG may be useful in treating HNSCC and breast carcinoma because it can exert both antiproliferative and antiangiogenic activities.
EGCG potential as a pro-apoptotic agent
Cell Cycle Dysregulation by Green Tea Polyphenol Epigallocatechin-3-Gallate.
Source: Biochem Biophys Res Commun. 2000 Aug 28;275(2):328-34
Affiliation: Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA.
Abstract: This study, employing A431 cells, provides evidence for the involvement of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery during cell cycle deregulation by EGCG. The study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is irreversible process ultimately resulting in an apoptotic cell death. The study suggests that the naturally occurring agents such as green tea polyphenols which may inhibit cell cycle progression could be developed as potent anticancer agents for the management of cancer.
Growth Inhibitory and Antimetastatic Effect of Green Tea polyphenols in vitro and in vivo
Growth Inhibitory and Antimetastatic Effect of Green Tea polyphenols on Metastasis-Specific Mouse Mammary Carcinoma 4T1 Cells In Vitro and In Vivo Systems
Source: Clin Cancer Res. 2005 Mar 1;11(5):1918-27
Affiliation: Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
Abstract: This study examined the effect of green tea polyphenols (GTP) on growth and metastasis of highly metastatic mouse mammary carcinoma 4T1 cells in vitro and in vivo systems. 4T1 cells were treated with (-)-epigallocatechin-3-gallate (EGCG), and the effect was determined on cellular proliferation, induction of apoptosis, proapoptosis, and antiapoptotic proteins of Bcl-2 family, and caspase 3 and poly(ADP-ribose) polymerase activation following 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Western blot analysis. This study suggests that GTP have the ability to prevent the development of breast cancer and its metastasis; however, further in vivo studies are required to identify the molecular targets.
Growth inhibitory effect of EGCG on human breast cancer cells
Inhibition of Cyclin-Dependent Kinases 2 and 4 Activities as well as Induction of Cdk Inhibitors p21 and p27 During Growth Arrest of Human Breast Carcinoma Cells by (-)-Epigallocatechin-3-Gallate.
Source: J Cell Biochem. 1999 Oct 1;75(1):1-12
Affiliation: Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Abstract: This study investigated the effects of EGCG and other catechins on the cell cycle progression. DNA flow cytometric analysis indicated that 30 microM of EGCG blocked cell cycle progression at G1 phase in asynchronous MCF-7 cells. In addition, cells exposed to 30 microM of EGCG remained in the G1 phase after release from aphidicolin block. Over a 24-h exposure to EGCG, the Rb protein changed from hyper- to hypophosphorylated form and G1 arrest developed. The results suggest that EGCG either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins such as Cdk2 and Cdk4 or mediates the induction of Cdk inhibitor p21 and p27.
Herbal medicine in cancer prevention
New TNF-Alpha Releasing Inhibitors as Cancer Preventive Agents from Traditional Herbal Medicine and combination Cancer prevention Study with EGCG and Sulindac or Tamoxifen.
Source: Mutat Res. 2003 Feb-Mar;523-524:119-25.
Affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-Cho, Tokushima 770-8514, Japan. hfujiki@ph.bunri-u.ac.jp
Abstract: This study review two important results with EGCG: the synergistic effects of EGCG with sulindac or tamoxifen on cancer preventive activity in PC-9 cells, and cancer prevention of intestinal tumor development in multiple intestinal neoplasia (Min) mice by co-treatment using EGCG with sulindac. The study reports new findings on additional gene expression resulting from co-treatment with EGCG and sulindac in PC-9 cells compared with gene expression by EGCG alone or sulindac alone. The results indicate that, with the continuing spread of cancer chemoprevention as a fundamental medical strategy, both clinicians and researchers should take a closer look at herbal medicine.
Investigation of various cellular anti- cancer mechanisms of tea polyphenols
Mechanisms of Cancer Prevention by Green and Black Tea Polyphenols
Source: Anticancer Agents Med Chem. 2006 Sep;6(5):389-406
Affiliation: Department of Biology, University of Northern Iowa, Cedar Falls, IA 50614, USA. lisa.beltz@uni.edu
Abstract: This study delineates the wide range of mechanisms by which epigallocatechin gallate (ECGC) and other green and black tea polyphenols inhibit cancer cell survival. EGCG suppressed androgen receptor expression and signalling via several growth factor receptors. Polyphenols reduced angiogenesis in part by decreasing vascular endothelial growth factor production and receptor phosphorylation. Recent work demonstrated that EGCG reduced dihydrofolate reductase activity, which would affect nucleic acid and protein synthesis. It also acted as an aryl hydrocarbon receptor antagonist by directly binding the receptor's molecular chaperone, heat shock protein 90. In conclusion, green and black tea polyphenols act at numerous points regulating cancer cell growth, survival, and metastasis, including effects at the DNA, RNA, and protein levels.
Molecular basis of EGCG effects in breast cancer cells
Tea polyphenol (-)-Epigallocatechin 3-Gallate Suppresses Heregulin-Beta1-Induced Fatty Acid Synthase Expression in Human Breast Cancer Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Cascade Signaling
Source: J Agric Food Chem. 2007 Jun 27;55(13):5030-7.
Affiliation: Department of Seafood Science, National Kaohsiung Marine University, No. 142, Hai-Chuan Road, Nan-Tzu, Kaohsiung 811, Taiwan.
Abstract: This study examined the effects of EGCG on FAS expression modulated by another member of the erbB family, that is, HER2 or HER3. It identified that heregulin-beta1 (HRG-beta1), a HER3 ligand, stimulated dose-dependent FAS expression in breast cancer cell lines MCF-7 and AU565, but not MDA-MB-453. The time-dependent increase in FAS expression after HRG-beta1 stimulation was also observed in MCF-7 cells, and this up-regulation was de novo RNA synthesis dependent. The results indicate that EGCG may be useful in the chemoprevention of breast carcinoma in which FAS overexpression results from HER2 or/and HER3 signaling.
Multiple mechanistic aspects of anti-caner effects of green tea and epidemiological evidence
Cancer Prevention with Green Tea and Monitoring by a New Biomarker, hnRNP B1.
Source: Mutat Res. 2001 Sep 1;480-481:299-304
Affiliation: Saitama Cancer Center, Ina, Kitaadachi-gun, Saitama 362-0806, Japan. hfujiki@cancer-c.pref.saitama.jp
Abstract: This study briefly reviews four topics related to mechanisms of action of tea polyphenols: (I) identification of the genes commonly affected by EGCG, as demonstrated by Clontech's Atlas cDNA Expression Array; (II) the significance of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) as a new biomarker for early detection of lung cancer, and inhibition of its expression by EGCG; (III) the synergistic or additive effects of EGCG with the cancer preventive agents, sulindac and tamoxifen, on induction of apoptosis in PC-9 cells and on inhibition of intestinal tumor development in multiple intestinal neoplasia (Min) mice; (IV) the results of a 10 year prospective cohort study demonstrating the effectiveness of daily consumption of green tea in preventing cancer, and a prototype study for developing green tea beverage as cancer preventive.
Novel molecular mechanism involved in inhibition of invasiveness of breast cancer cells
Activation of FOXO3a by the Green Tea Polyphenol Epigallocatechin-3-Gallate Induces Estrogen Receptor Alpha Expression Reversing Invasive phenotype of Breast Cancer Cells.
Source: Cancer Res. 2007 Jun 15;67(12):5763-70
Affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Abstract: This study shows that EGCG treatment of Her-2/neu-driven mammary tumor cells alters the expression of key regulators in the epithelial to mesenchymal transition (EMT) pathway, reducing invasive phenotype. Specifically, the epithelial genes E-cadherin, gamma-catenin, MTA3, and estrogen receptor alpha (ERalpha) were up-regulated by EGCG, whereas the proinvasive snail gene was down-regulated. Consistently, EGCG inhibited branching colony growth and invasion in Matrigel. EGCG treatment similarly inhibited invasive phenotype of mouse mammary tumor cells driven by Nuclear Factor-kappaB c-Rel and protein kinase CK2, frequently found overexpressed in human breast disease. This study also identifies, for the first time, a role for FOXO3a in the inhibition of invasive phenotype in breast cancer cells with active ERalpha signaling and elucidate a novel mechanism whereby EGCG represses EMT of breast cancer cells.
Review on EGCG role in cancer
Reading the Tea Leaves: Anticarcinogenic Properties of (-)-Epigallocatechin-3-Gallate.
Source: Mayo Clin Proc. 2007 Jun;82(6):725-32.
Affiliation: Department of Biology, Winona State University, Winona, MN 55987, USA.
Abstract: This study that is based on a comprehensive search of the PubMed database and other secondary data sources indicates that EGCG functions as an antioxidant, preventing oxidative damage in healthy cells, but also as an antiangiogenic agent, preventing tumors from developing a blood supply needed to grow larger. Furthermore, EGCG may stimulate apoptosis in cancerous cells by negatively regulating the cell cycle to prevent continued division. Finally, EGCG exhibits antibacterial activity, which may be implicated in the prevention of gastric cancer. Although in vitro research of the anticarcinogenic properties of EGCG seems promising, many diverse and unknown factors may influence its in vivo activity in animal and human models. Some epidemiological studies suggest that green tea compounds could protect against cancer, but existing data are inconsistent. Several clinical trials with green tea derivatives are ongoing, and further research should help to clarify the clinical potential of EGCG for chemoprevention and/or chemotherapy applications.
Role of tea polyphenols in regulating various molecular mechanisms associated with cancer
Potential Molecular Targets of Tea Polyphenols in Human Tumor Cells: Significance in Cancer Prevention
Source: In Vivo. 2002 Nov-Dec;16(6):397-403
Affiliation: Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Departments of Interdisciplinary Oncology and Biochemistry & Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Abstract: The most abundant and popular compound studied in tea research is (-)-epigallocatechin-3-gallate (EGCG), which acts as a powerful antioxidant and can inhibit a number of tumor cell proliferation- and survival-related proteins. Epidemiological studies have shown decreased cancer occurrence in individuals who drink green tea regularly. This study explains that role of tea polyphenols which inhibit the activities of many tumor-associated protein kinases, including epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, mitogen-activated protein kinase, and IkB kinase. Tea polyphenols have also been found to inhibit some cancer-related proteins that regulate DNA replication and transformation. This study suggests that by understanding the in vivo concentrations of tea polyphenols required to inhibit each of these activities, we may start to sort out in the future the mechanisms responsible for the cancer-preventive effects of tea.
EGCG and Lung Cancer
Synergistic Effects of (--)-Epigallocatechin gallate with (--)-Epicatechin, Sulindac, or Tamoxifen on Cancer-Preventive Activity in the Human Lung Cancer Cell Line PC-9.
Source: Cancer Res. 1999 Jan 1;59(1):44-7
Affiliation: Saitama Cancer Center Research Institute, Japan.
Abstract: This study shows that incorporation of [3H](-)-epigallocatechin gallate (EGCG) into human lung cancer cell line PC-9 can be significantly enhanced by (-)-epicatechin, an inert tea polyphenol without a galloyl moiety. (-)-Epicatechin enhanced apoptosis, growth inhibition of PC-9 cells, and inhibition of tumor necrosis factor-alpha release from BALB/c-3T3 cells by EGCG and other tea polyphenols with a galloyl moiety in a dose-dependent manner. This paper reports that whole green tea is a more effective mixture of tea polyphenols for cancer prevention in humans than EGCG alone and that it is even more effective when it is used in combination with other cancer preventives.
EGCG and Melanoma
Anti-Proliferative and Pro-apoptotic Effects of (-)-Epigallocatechin-3-Gallate on Human Melanoma: Possible Implications for the Chemoprevention of Melanoma
Source: Int J Cancer. 2005 Apr 20;114(4):513-21.
Affiliation: Department of Dermatology, University of Wisconsin and William S. Middleton Veterans Memorial Hospital, Madison, WI 53706, USA.
Abstract: This study examined the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, in two human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM). EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. The data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.
EGCG and Prostate Cancer
Molecular Pathway for (-)-Epigallocatechin-3-Gallate-Induced Cell Cycle Arrest and Apoptosis of Human Prostate Carcinoma Cells
Source: Arch Biochem Biophys. 2003 Feb 1;410(1):177-85
Affiliation: Department of Urology, Jim & Eillen Dicke Research Laboratory, Case Western Reserve University, The Research Institute of University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Abstract: This study showed that green tea polyphenols exert remarkable preventive effects against prostate cancer in a mouse model and many of these effects are mediated by the ability of polyphenols to induce apoptosis in cancer cells. The study tested a hypothesis that EGCG-mediated cell cycle dysregulation and apoptosis is mediated via modulation of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery. The results suggest that EGCG causes an induction of G1 phase ckis, which inhibits the cyclin-cdk complexes operative in the G0/G1 phase of the cell cycle, thereby causing an arrest, which may be an irreversible process ultimately leading to apoptotic cell death. This is the first systematic study showing the involvement of each component of cdk inhibitor-cyclin-cdk machinery during cell cycle arrest and apoptosis of human prostate carcinoma cells by EGCG.
Green Tea Polyphenols Block Endotoxin-Induced Tumor Necrosis Factor-Production and Lethality in a Murine Model
Source: J Nutr. 1998;128(12):2334-40.
Affiliation: Graduate Program in Nutritional Sciences, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA.
Abstract: This study postulated that green tea polyphenols regulate tumor necrosis factor-alpha (TNFalpha) gene expression by modulating NF-KB activation through their antioxidant properties. Tumor necrosis factor-alpha(TNFalpha) plays a pivotal role in inflammations. The study concludes that the anti-inflammatory mechanism of green tea polyphenols is mediated at least in part through down-regulation of TNFalpha gene expression by blocking NF-KB activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.
EGCG and Stomach Cancer
Mechanistic Aspects of Green Tea as a Cancer Preventive: Effect of Components on Human Stomach Cancer Cell Lines
Source: Jpn J Cancer Res. 1999 Jul;90(7):733-9
Affiliation: Saitama Cancer Center Research Institute.
Abstract: The aim of this study was to understand the mechanisms of anticarcinogenesis through the examination of growth inhibition by EGCG in human stomach cancer cell lines established at Seoul National University (SNU cell lines). Inhibition by EGCG of [3H]thymidine incorporation into eight SNU cell lines was observed in relation to transforming growth factor-beta (TGF-beta) responsiveness. This study demonstrates that EGCG and other tea polyphenols may interact with various transcription factors, in addition to AP-1 and NF-kappa B, in nuclei of various cells, resulting in inhibition of TNF-alpha gene expression and TNF-alpha release.
Mechanisms of Cancer Prevention by Tea Polyphenols Based on Inhibition of TNF-Alpha Expression
Source: Biofactors. 2000;13(1-4):67-72
Affiliation: Saitama Cancer Center Research Institute, Japan.
Abstract: This animal study with TNF-alpha-deficient mice has revealed that TNF-alpha is an essential factor in tumor promotion. The study found that EGCG dose-dependently inhibited AP-1 and NF-kappaB activation in BALB/3T3 cells treated with okadaic acid, resulting in inhibition of TNF-alpha gene expression. Furthermore, treatment with 0.1% green tea extract in drinking water reduced TNF-alpha gene expression as well as TNF-alpha protein level in the lung of TNF-alpha transgenic mice; and IL-1beta and IL-10 gene expression in the lung was also inhibited by treatment with green tea extract, indicating that green tea inhibits both TNF-alpha and the cytokines induced by TNF-alpha in organs. The study reports the synergistic effects of EGCG and cancer preventive agents such as tamoxifen and sulindac, on cancer preventive activity. All these results show that green tea is efficacious as a non-toxic cancer preventive for humans.
Specific micronutrient combination inhibits metastasis of melanoma cancer to the lungs
Inhibition of Pulmonary Metatasis of Melanoma B16FO Cells in C57BL/6 Mice by a Nutrient Mixture Consisting of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract
Source: Experimental Lung Research, 2006 Nov-Dec; 32(10):517-530.
Affiliation: Dr Rath Research Institute, Santa Clara, CA, USA
Abstract: The primary objective of this animal study was to investigate whether these natural components applied as a synergistic mixture (NM) could inhibit experimentally induced lung metastases in C57BL/6 female mice injected with melanoma B16FO cells. In mice supplemented with NM through the diet the number of metastatic colonies in the lungs was reduced by 63%. In mice who received NM through ip and iv injection the number of lung metastases was reduced by 86%. In mice injected with melanoma cells pretreated with NM no lung metastases were detected, the metastasis was inhibited by 100%. The results of this study show that this nutrient mixture administered in a diet was effective in a significant inhibition of metastasis of B16FO melanoma cells to the lungs. By exposure to higher concentrations of NM, such as obtained through iv or ip delivery, an enhanced inhibitory effect was obtained (up to 86%). It is important to note that the exposure of tumor cells to NM before their injection to the mice completely prevented development of lung tumors (100% inhibition of metastasis). These findings together with earlier results provided by Dr. Rath’s research team clearly indicate that natural nutrient combination (NM) has a high potential in preventing cancer metastasis.
http://www.drrathresearch.org/lab_research/study_c_metas_melanoma_010507.html
http://www.drrathresearch.org/lab_research/metas_melanoma_010507.pdf
Anti-proliferative and anti-cancer effects of specific micronutrient combination
A Specific Combination of Ascorbic Acid, Lysine, Proline and Epigallocatechin Gallate Inhibits Proliferation and Extracellular Matrix Invasion of Various Human Cancer Cell Lines (2003)
Source: Research Communications in Pharmacology and Toxicology: Emerging Drugs, 2:37-5, 2003.
Affiliation: Dr Rath Research Institute, Santa Clara, CA, USA
Abstract: This study demonstrates significant anti-proliferative and anti-metastatic effects in vitro against some human cancer cell lines (breast, colon, and melanoma) using a specific combination of ascorbic acid, proline, and lysine. The addition of epigallocatechin gallate (EGCG) to the nutrient mixture enhanced the inhibitory effect on both cellular proliferation and invasion. The proliferation of breast cancer cells (MDA-MB-231) in the presence of AA, P, L and 20 µg/ml of EGCG was reduced to 74%. The proliferation of colon cancer cells (HCT 116) was reduced to 69%, compared to the non-supplemented medium. The increase in concentration of EGCG to 50 µg/ml did not cause much further reduction in the cell number of breast cancer cells, but it did reduce the proliferation of colon cancer cells to 4.6% and melanoma cells to 30% of the control. These results are significant in showing the great potential of the control of cancer growth and metastasis using a safe natural nutrient approach.
http://www.drrathresearch.org/lab_research/study_c_specific_combo_human_cancer_cell.html
http://www.drrathresearch.org/lab_research/lab_research_printable/study_c_specific_human_cancer.pdf
Inhibitory effects of synergy of micronutrients in ovarian cancer
Inhibition of Matrix Metalloprotenase-2 Secretion and Invasion by Human Ovarian Cancer Line SK-OV-3 with Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract
Source: Journal of Obstetrics and Gynaecology Research, 2006, 32(2):148-154.
Affiliation: Dr Rath Research Institute, Santa Clara, CA, USA
Abstract: This study investigated the effect of Dr. Rath’s nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on human ovarian cancer cells SK-OV-3 by measuring: cell proliferation, modulation of MMP-2 and –9 secretion, and cancer cell invasive potential. The tested NM inhibited MMP-2 secretion in a dose-dependent fashion with virtual total inhibition at 50 µg/ml NM concentration. Invasion of human ovarian cancer cells through Matrigel decreased in a dose-dependent fashion, with 90% inhibition at 500 µg/ml NM and 100% inhibition at 1000 µg/ml NM (p<0.0001). The combination of lysine, proline, arginine, ascorbic acid, and green tea extract inhibited critical steps in cancer development and spread, such as MMP secretion and invasion, indicating its potential as a treatment modality against ovarian cancer.
http://www.drrathresearch.org/lab_research/study_c_ovarian_cancer_SKOV3_111706.html
http://www.drrathresearch.org/lab_research/ovarian_cancer_SK-OV-3.pdf
Specific micronutrient combination inhibits tumor growth and demonstrates therapeutic potential in lung cancer
In Vivo and In Vitro Anti-tumor Effect of a Unique Nutrient Mixture on Lung Cancer Cell Line A-549
Source: Experimental Lung Research, 2006, 32:1-13.
Affiliation: Dr Rath Research Institute, Santa Clara, CA, USA
Abstract: The study investigated the effect of specific nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on the tumor growth of human lung carcinoma cell A-549 xenografts in athymic nude mice. Additionally, the study tested the in vitro antitumor effect of NM on lung carcinoma A-549 cells by measuring: cell proliferation by MTT assay, MMP-2 and –9 secretion by gelatinase zymography and cell invasion through Matrigel. Dr. Rath’s nutrient mixture (NM) strongly suppressed the growth of tumors without adverse effects in nude mice; tumor weight was reduced by 44% (p=0.0001) and tumor burden was reduced by 47% (p<0.0001) with supplementation. The NM also inhibited the secretion of both MMPs in a dose-dependent fashion with virtual total inhibition at 500 µg/ml concentration. The invasion of human lung carcinoma cells through Matrigel was significantly reduced at 100 µg/ml (64%) and totally inhibited at 500-µg/ml concentration of NM (p=0.01). These results suggest NM as a potential non-toxic therapeutic agent for lung cancer.
http://www.drrathresearch.org/lab_research/study_c_lungcancer_121106.html
http://www.drrathresearch.org/lab_research/lung_cancer_a549.pdf
Vitamin C and Bladder Cancer
Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women
Source: Am J Epidemiol. 2002 Dec 1;156(11):1002-10
Affiliation: Department of Epidemiology and Surveillance Research, American Cancer Society, National Home Office, Atlanta, GA 30329-4251, USA. eric.jacobs@cancer.org
Abstract: The authors of this study examined the association between use of individual vitamin C and vitamin E supplements and bladder cancer mortality among 991,522 US adults in the Cancer Prevention Study II (CPS-II) cohort. Regular vitamin C supplement use (15 or more times per month) was not associated with bladder cancer mortality, regardless of duration (rate ratio (RR) = 0.91, 95% confidence interval (CI): 0.68, 1.20 for <10 years' use; RR = 1.25, 95% CI: 0.91, 1.72 for >or=10 years' use). Regular vitamin E supplement use for 10 years or longer was associated with a reduced risk of bladder cancer mortality (RR = 0.60, 95% CI: 0.37, 0.96), but regular use of shorter duration was not (RR = 1.04, 95% CI: 0.77, 1.40). Results support the hypothesis that long-duration vitamin E supplement use may reduce the risk of bladder cancer mortality.
Are Retinol, Vitamin C, Vitamin E, Folate and Carotenoids Intake Associated with Bladder Cancer Risk? Results from the Netherlands Cohort Study
Source: British Journal of Cancer (2001) 85, 977–983.
Affiliation: Department of Epidemiology, Maastricht University, Maastricht; Department of Nutritional Epidemiology, TNO Nutrition and Food Research, Zeist, The Netherlands
Abstract: The cohort study of 120 852 subjects aged 55–69 years at baseline (1986) conducted in the Netherlands examined the association between vitamins and carotenoids intake, vitamin supplement use, and bladder cancer incidence. Exposure status was measured with a food-frequency questionnaire. The study concludes that dietary or supplemental intake of vitamin A, vitamin C, vitamin E, and intake of folate, and most carotenoids are not associated with bladder cancer. In this study, only β-cryptoxanthin intake appeared to be inversely associated.
Vitamin C and Breast Cancer
Ascorbate (Vitamin C) Induces Cell Death Through the Apoptosis-Inducing Factor in Human Breast Cancer Cells
Source: Oncol Rep. 2007 Oct;18(4):811-5
Affiliation: Research Center for Women's Diseases, Division of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Korea.
Abstract: This study demonstrates that ascorbate induces cell death through the apoptosis-inducing factor (AIF) in the human breast cancer cell lines, SK-BR3 and Hs578T, but not in a normal breast cell line, Hs578. Ascorbate treatment caused the nuclear translocation of AIF, which is retained in the mitochondria in healthy cells, but caspase cleavage is not induced. Moreover, MG132, an inhibitor of AIF release from mitochondria, blocked the induction of cell death. Furthermore, cells that had been treated with human AIF-specific siRNA resisted cell death induced by ascorbate, implying that the translocation of AIF from mitochondria to the nucleus is responsible for ascorbate-mediated cell death.
Association Between Breast Cancer and Vitamin C, Vitamin E and Selenium Levels: Results of a Case-Control Study in India.
Source: Asian Pac J Cancer Prev. 2005 Apr-Jun;6(2):177-80
Affiliation: Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India.
Abstract: This hospital based case-control study conducted in India examined the associations of vitamin C, vitamin E and selenium with breast cancer. One hundred and sixty breast cancer patients and an equal number of normal healthy individuals constituted the study population. Venous blood was collected from the cases and controls for estimation of vitamin C, vitamin E and selenium utilizing standard procedures. The results of the present study thus indicated a strong association of vitamin C, vitamin E and selenium with breast cancer in the Indian population.
Meta-Analysis of Studies on Breast Cancer Risk and Diet, the Role of Fruit and Vegetable Consumption and the Intake of Associated Micronutrients.
Source: European Journal of Cancer, Volume 36, Issue 5, p. 636–646, (March 2000)
Affiliation: Division of Epidemiology and Biostatics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy,1 Bremer Institut für Praeventionsforschung und Sozialmedizin (BIPS), Gruenenstrasse 120, 28199 Bremen, Germany2
Abstract: A meta-analysis was carried out, in order to summarise published data on the relationship between breast cancer, fruit and vegetable consumption and/or the intake of beta-carotene and vitamin C. Relative risks were extracted from 26 published studies from 1982 to 1997. Random and fixed effects models were used. Between studies, heterogeneity was found for vegetables, fruit, vitamin C but not for beta-carotene. This analysis confirms the association between intake of vegetables and, to a lesser extent, fruits and breast cancer risk from published sources.
http://linkinghub.elsevier.com/retrieve/pii/S0959804900000228
Vitamin C and Cancer
Ascorbic Acid in the Prevention and Treatment of Cancer
Source: Alternative Medicine Review, Volume 3, Number 3, 1998
Affiliation: Technical Advisor, Thorne Research, Inc.; Associate Editor, Alternative Medicine Review
Abstract: Vitamin C in high dosages appears to be safe for the majority of individuals. Extensive epidemiological evidence points to the capacity of ascorbic acid to prevent cancer at a number of sites. In addition, some of the limited studies which have been conducted on the use of high dose ascorbate in the treatment of cancer have yielded promising results. The study concludes that “while vitamin C alone may not be enough of an intervention in the treatment of most active cancers, since it appears to improve quality of life and extend survival time, it should be considered as part of a treatment protocol for all patients with cancer, whether they have chosen a primarily orthodox, alternative medical, or complementary approach.”
Pharmacologic Ascorbic Acid Concentrations Selectively Kill Cancer Cells: Action as a Pro-Drug to Deliver Hydrogen Peroxide to Tissues
Source: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12
Affiliation: Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract: This study goals were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. The data indicates that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2), and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H(2)O(2) may be beneficial.
Vitamin C and Treatment of Cancer: Part I. Abstracts and Commentary from the Scientific Literature.
Source: Townsend Letter for Doctors & Patients - May 1997
Affiliation:
Abstract: This is a review of the scientific literature as it pertains to the impact of vitamin C on cancer. The questions, "What works?" and "How might it be applied?" were the motivational ones behind this review. Each review includes well-designed studies from peer-reviewed journals. Original journal citations are given, along with capsule descriptions of the original scientific abstracts. This review article notes that approximately 90 studies have been done on the role of vitamin C in cancer prevention, with most finding statistically significant effects. Protective effects have been shown for cancers of the pancreas, oral cavity, stomach, esophagus, cervix, rectum, breast, and lung.
Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later.
Source: Integrative Cancer Therapies 2005; 4(1); pp.32-44
Affiliation: University of Puerto Rico, Medical Sciences Campus, Graduate School of Public Health, Department Human Development, Nutrition Program, PO Box 365067, San Juan, PR. mgonzalez@rcm.upr.edu
Abstract: This is a follow-up review of the 1979 article by Cameron, Pauling, and Leibovitz published in Cancer Reasearch. The objective of this review is to provide an updated scientific basis for the use of ascorbic acid, especially intravenously as adjuvant treatment in pharmacological nutritional oncology. In this updated version, the authors address general aspects of ascorbic acid and cancer that have been presented before, while reviewing, analyzing, and updateing new existing literature on the subject. In addition, they present and discuss their own mechanistic hypothesis on the effect of ascorbic acid on the cancer cell.
Intravenous Ascorbic Acid: Protocol for Its Application and Use
Source: Puerto Rico Health Sciences Journal (2003) 22:3, 287-290
Affiliation: Center for the Improvement of Human Functioning, Biocommunications Research Institute, Wichita, KS, USA.
Abstract: This publication describes a clinical protocol that has been developed over the past twenty years utilizing high dose IV AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects. Ascorbate administered in pharmacological doses enhances various parameters associated with better prognosis. There is also evidence that physiologically attainable concentrations by intravenous administration are selectively toxic to cancer; contrary to the limited levels of ascorbate that can be reached by oral intakes. Moreover, there is evidence of synergism between the conventional methods for cancer treatment (surgery, radiation and chemotherapy) when utilized with ascorbate.
Rethinking Vitamin C and Cancer: An Update on Nutritional Oncology
Source: Cancer Prevention International (1998) 3: 215-234
Affiliation: University of Puerto Rico, Medical Sciences Campus, Graduate School of Public Health, Department Human Development, Nutrition Program, PO Box 365067, San Juan, PR. mgonzalez@rcm.upr.edu
Abstract: This article is an attempt to ease the existing controversy while providing an updated scientific basis for the use of vitamin C in nutritional oncology. This article addresses general aspects of vitamin C and cancer, while reviewing and analyzing existing literature on the subject. In addition, presents and discusses hypothesis on the effect of vitamin C on cancer (solid tumors).
Intravenous Ascorbate as a Tumor Cytotoxic Chemotherapeutic Agent
Source: Medical Hypotheses (1995), 44, 207-213
Affiliation: Project RECNAC, Bio-Communications Research Institute, Wichita, Kansas 67219, USA
Abstract: This study shows that sufficient evidence exists to support the testing of intravenous AA for extended periods as a cytotoxic chemotherapy agent, in doses high enough to maintain plasma levels above those which have been found to be preferentially cytotoxic to tumor cells in vitro. In the presented study altogether, six patients have been infused intravenously with similar doses of AA over 8-h periods with no reported side-effects. In all cases, the patients had either been given no further therapeutic options by their oncologists, had refused further conventional treatment, or in one case, requested the use of AA in conjunction with standard chemotherapy. AA is relatively non-toxic and is preferentially cytotoxic to tumor cells at levels attainable in human plasma, at least in vitro. The study concludes that further research on the in vivo effects and mechanism of AA’s preferential cytotoxicity need to be performed.
Intravenously Administered Vitamin C as Cancer Therapy: Three Cases
Source: Canadian Medical Association Journal 2006;174(7):937-42
Affiliation: Molecular and Clinical Nutrition Section, Bldg. 10, Rm 4D52–MSC 1372, National Institutes of Health, Bethesda MD 20892–1372; MarkL@mail.nih.gov
Abstract: This study found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. Accumulated data confer some degree of biological and clinical plausibility to the notion that high-dose intravenous vitamin C therapy may have anti-tumour effects in certain cancers. Recent findings show that only high-dose intravenous, but not oral, vitamin C therapy results in very high plasma vitamin C concentrations (e.g., 14 000 µmol/L). At these concentrations, the vitamin is toxic to some cancer cells, possibly because at these concentrations the vitamin is a pro-drug for hydrogen peroxide formation in extracellular fluid. The study examined clinical details of each cancer case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumor pathology was verified by pathologists at the NCI who were unaware of diagnosis or treatment. In light of recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed.
The Orthomolecular Treatment of Cancer. Clinical Trial of High-Dose Ascorbic Acid Supplements in Advanced Human Cancer.
Source: Chemico-Biological Interactions, October 1974; Volume 9, Issue 4, Pages 285-315
Affiliation: Department of Clinical Research, Vale of Leven District General Hospital, Dunbartonshire; Department of Medicine, Hairmyres Hospital, LanarkshireScotland,1 Institute of Orthomolecular Medicine, Menio Park, Calif.U.S.A. 2
Abstract: This study reports the clinical response of fifty consecutive advanced cancer patients to the continuous administration of large doses of ascorbic acid. It concludes that this simple and safe form of treatment is of definite value in the palliation of terminal cancer. The findings suggest that it should be employed as a standard supportive measure to reinforce established methods of treatment in the general management of earlier and more favorable cases.
The Orthomolecular Treatment of Cancer: III. Reticulum Cell Sarcoma: Double Complete Regression Induced by High-Dose Ascorbic Acid Therapy.
Source: Chemico-Biological Interactions, November 1975; Volume 11, Issue 5, , p. 387-393
Affiliation: Department of Medicine, Hairmyres Hospital, Lanarkshire, Scotland, Vale of Leven District General Hospital, Alexandria, Dumbartonshire, Scotland, the Linus Pauling Institute of Science and Medicine, Menlo Park, Calif., U.S.A.
Abstract: This study describes the response of a patient with histologically proven reticulum cell sarcoma to no treatment other than large doses of ascorbic acid. At the time of first diagnosis, the disease was widely disseminated, and a very dramatic regression of all parameters of disease activity was induced by the continuous administration of large doses of ascorbic acid. Reduction in dosage some months later coincided with reactivation of the disease process. The reinstitution of regular high-dose ascorbic acid therapy induced a second complete remission.
http://www.sciencedirect.com/science?=b1c35672c38f1fbe4d8a88ca45801967
Supplemental Ascorbate in the Supportive treatment of Cancer: Prolongation of Survival Times in Terminal human Cancer
Source: Proceedings of the National Academy of Sciences, October 1, 1976 vol. 73 no. 10, 3685-3689
Affiliation: Vale of Leven District General Hospital, Loch Lomondside, G83 OUA, Scotland;1 Linus Pauling Institute of Science and Medicine, 2700 Sand Hill Road, Menlo Park, California 940252
Abstract: Cancer patients are significantly depleted of ascorbic acid, and in the author’s opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. This study presents the results of a clinical trial in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days).
Protocol for the Use of Vitamin C in the Treatment of Cancer
Source: Med Hypotheses. 1991 Nov;36(3):190-4
Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, California 94306.
Abstract: A protocol for the use of vitamin C in the treatment of cancer, has been developed over a number of years in Vale of Leven Hospital, Scotland. Clinical experience has shown this protocol to be both safe and efficient, and provides general guidance to physicians unfamiliar with this therapeutic approach. It recommends that all cancer patients treated in this fashion be given an initial course of intravenous ascorbate followed by a maintenance oral dose to be continued indefinitely thereafter. The importance of continuous as opposed to intermittent administration is emphasized.
Intravenous Vitamin C as a Chemotherapy Agent: a Report on Clinical Cases.
Source: PR Health Sci J. 2004 Jun;23(2):115-8.
Affiliation: Center for the Improvement of Human Functioning, RENAC Project, Wichita, KS, USA.
Abstract: A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma, colorectal cancer, pancreatic cancer, Non-Hodgkin's lymphoma and breast cancer. Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6 phosphate dehydrogenase deficiency before administering intravenous vitamin C in order to prevent hemolysis.
Vitamin C and cancer revisited.
Source: Procedings of the National Academy of SciencesUSA, 2008;105(32):11037-11038.
Affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. balz.frei@oregonstate.edu
Abstract: The potential for vitamin C to destroy cancerous cells is substantial, and the regimen appears to be well tolerated, but there is still a “missing link,” Dr. Frei says. For vitamin C to act as a pro-oxidant and produce hydrogen peroxide, a protein that contains “redox-active” metal ions such as copper or iron must be present. Researchers still don’t know exactly what that metal-containing protein is, but they believe it will be the key to any anticancer effect of vitamin C.
Pharmacologic Doses of Ascorbate Act as a Pro-oxidant and Decrease Growth of Aggressive Tumor Xenografts in Mice
Source: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9. Epub 2008 Aug 4
Affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, and Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract: This study shows that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.
Vitamin C and Colon Cancer
Associations of Micronutrients with Colon Cancer Risk in African Americans and Whites: Results from the North Carolina Colon Cancer Study
Source: Cancer Epidemiology, Biomarkers & Prevention, 2003, Vol. 12, 8, pp. 747-754
Affiliation: Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,1 Lineberger Comprehensive Cancer Center, Cancer Prevention and Control Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,2 School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,3 Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington 98109,4 Department of Epidemiology, University of Washington, Seattle, Washington 98105,5 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,6
Abstract: This report describes associations of micronutrients with colon cancer risk in African Americans and whites using data from a case-control study in North Carolina. Incident cases of histologically confirmed colon cancer, age 40-80 years (n = 613), and matched controls (n = 996) were interviewed in person to elicit information on potential colon cancer risk factors. Micronutrient exposure included food sources and dietary supplements, such as vitamin C, E, beta–carotene, and calcium. These results suggest that at high intakes, micronutrients commonly found in plant and other foods (in particular, β-carotene, vitamin C, and calcium in whites and vitamins C and E in African Americans) exhibit independent associations consistent with 30-70% reductions in colon cancer risk.
Case-Control Study on Colorectal Cancer in Belgium. Preliminary Results
Source: Social and Preventive Medicine, March 1986; Volume 21, Number 2, Pages 81-82
Affiliation: Centre international de recherche sur le cancer, 150 Cours Albert Thomas, F-69372 Lyon
Abstract: Preliminary results of a case-control study in two Belgian provinces, involving 1207 cases of colorectal cancer and 3521 population controls show that an excess risk of colon cancer is associated with low intake of calories, proteins and lipids. High intake of vitamin C, vitamin B, and fiber have a protective effect on both colon and rectal cancer. When foods were examined, most vegetables were found to have protective virtues, noticeable in all subgroups.