How PPs Fight Cancer

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Action Pathways of Anticancer Agents

This diagram shows the events that occur in the transformation of normal cells into an expanding (and metastasizing) mass of malignant cells (tumor). They include the initial transforming event, which involves DNA mutation and often chronic inflammation; promotion; and then progression of the tumor. Polyphenols block multiple points in this pathway.

Pomegranate Extract

Pomegranate extract (particularly the punicaligans and ellagic acid polyphenols) have been shown to block both tumor growth and metastasis through multiple mechanisms.

Fruit Polyphenol

The above diagram demonstrates how various fruits and vegetables slow the progression of and even halt various cancers through epigenetic mechanisms by increasing DNA methylation, modifying histones, or both.

Curcumin Blocks Cancer

Curcumin blocks malignant transformation, proliferation, and metastasis of various tumors through multiple mechanisms.

There is a wealth of data to support the anticancer benefits of these and other polyphenols. The most extensively documented are those above, EGCG, T-res, and Silymarin, all found in Dr. Flam’s Natural Supplements.

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Adwan, L., & Zawia, N. H. (2013). Epigenetics: A novel therapeutic approach for the treatment of alzheimer’s disease. Pharmacology and Therapeutics, 139(1), 41-50. Retrieved from www.scopus.com

Anderson, O. S., Sant, K. E., & Dolinoy, D. C. (2012). Nutrition and epigenetics: An interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. Journal of Nutritional Biochemistry, 23(8), 853-859. Retrieved from www.scopus.com

Angelo, L. S., & Kurzrock, R. (2009). Turmeric and green tea: A recipe for the treatment of B-chronic lymphocytic leukemia. Clinical Cancer Research, 15(4), 1123-1125. Retrieved from www.scopus.com

Bekir, J., Mars, M., Vicendo, P., Fterrich, A., & Bouajila, J. (2013). Chemical composition and antioxidant, anti-inflammatory, and antiproliferation activities of pomegranate (punica granatum) flowers. Journal of Medicinal Food, 16(6), 544-550. Retrieved from www.scopus.com

Berner, C., Aumüller, E., Gnauck, A., Nestelberger, M., Just, A., & Haslberger, A. G. (2011). Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food compounds. Annals of Nutrition and Metabolism, 57(3-4), 183-189. Retrieved from www.scopus.com

Buckingham, L. (2013). A look to the future: Cancer epigenetics Retrieved from www.scopus.com

Burdge, G. C., Hoile, S. P., & Lillycrop, K. A. (2012). Epigenetics: Are there implications for personalised nutrition? Current Opinion in Clinical Nutrition and Metabolic Care, 15(5), 442-447. Retrieved from www.scopus.com

Castelo-Branco, G., & Bannister, A. J. (2013). The epigenetics of cancer: From non-coding RNAs to chromatin and beyond. Briefings in Functional Genomics, 12(3), 161-163. Retrieved from www.scopus.com

Cencioni, C., Spallotta, F., Martelli, F., Valente, S., Mai, A., Zeiher, A. M., & Gaetano, C. (2013). Oxidative stress and epigenetic regulation in ageing and age-related diseases. International Journal of Molecular Sciences, 14(9), 17643-17663. Retrieved from www.scopus.com

Crescenti, A., Solà, R., Valls, R. M., Caimari, A., del Bas, J. M., Anguera, A., . . . Arola, L. (2013). Cocoa consumption alters the global DNA methylation of peripheral leukocytes in humans with cardiovascular disease risk factors: A randomized controlled trial. PLoS ONE, 8(6) Retrieved from www.scopus.com

Cuevas, A., Saavedra, N., Salazar, L. A., & Abdalla, D. S. P. (2013). Modulation of immune function by polyphenols: Possible contribution of epigenetic factors. Nutrients, 5(7), 2314-2332. Retrieved from www.scopus.com

Cycon, K. A., Mulvaney, K., Rimsza, L. M., Persky, D., & Murphy, S. P. (2013). Histone deacetylase inhibitors activate CIITA and MHC class II antigen expression in diffuse large B-cell lymphoma. Immunology, 140(2), 259-272. Retrieved from www.scopus.com

D’Arena, G., Simeon, V., De Martino, L., Statuto, T., D’Auria, F., Volpe, S., . . . De Feo, V. (2013). Regulatory T-cell modulation by green tea in chronic lymphocytic leukemia. International Journal of Immunopathology and Pharmacology, 26(1), 117-125. Retrieved from www.scopus.com

De, S., Shaknovich, R., Riester, M., Elemento, O., Geng, H., Kormaksson, M., . . . Michor, F. (2013). Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity. PLoS Genetics, 9(1) Retrieved from www.scopus.com

Delcurto, H., Wu, G., & Satterfield, M. C. (2013). Nutrition and reproduction: Links to epigenetics and metabolic syndrome in offspring. Current Opinion in Clinical Nutrition and Metabolic Care, 16(4), 385-391. Retrieved from www.scopus.com

Esatbeyoglu, T., Huebbe, P., Ernst, I. M. A., Chin, D., Wagner, A. E., & Rimbach, G. (2012). Curcumin-from molecule to biological function. Angewandte Chemie – International Edition, 51(22), 5308-5332. Retrieved from www.scopus.com

Farghali, H., Kutinová Canová, N., & Leki?, N. (2013). Resveratrol and related compounds as antioxidants with an allosteric mechanism of action in epigenetic drug targets. Physiological Research, 62(1), 1-13. Retrieved from www.scopus.com

Ferrari, K. J., & Pasini, D. (2013). Regulation and function of DNA and histone methylations. Current Pharmaceutical Design, 19(4), 719-733. Retrieved from www.scopus.com

Frazzi, R., Valli, R., Tamagnini, I., Casali, B., Latruffe, N., & Merli, F. (2013). Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation. International Journal of Cancer, 132(5), 1013-1021. Retrieved from www.scopus.com

Fu, S., & Kurzrock, R. (2010). Development of curcumin as an epigenetic agent. Cancer, 116(20), 4670-4676. Retrieved from www.scopus.com

Gerhauser, C. (2013). Cancer chemoprevention and nutri-epigenetics: State of the art and future challenges Retrieved from www.scopus.com

Gerhäuser, C. (2012). Cancer cell metabolism, epigenetics and the potential influence of dietary components – A perspective. Biomedical Research, 23(SPEC. ISSUE), 69-89. Retrieved from www.scopus.com

Hassler, M. R., Schiefer, A. -., & Egger, G. (2013). Combating the epigenome: Epigenetic drugs against non-hodgkin’s lymphoma. Epigenomics, 5(4), 397-415. Retrieved from www.scopus.com

Ho, A. S., Turcan, S., & Chan, T. A. (2013). Epigenetic therapy: Use of agents targeting deacetylation and methylation in cancer management. OncoTargets and Therapy, 6, 223-232. Retrieved from www.scopus.com

Hoon, H. D., Jeong, J. H., & Kim, H. J. (2009). Anti-proliferative and apoptosis induction activity of green tea polyphenols on human promyelocytic leukemia HL-60 cells. Anticancer Research, 29(4), 1417-1422. Retrieved from www.scopus.com

Huang, J. (2013). Thematic series: Epigenetics in stem cells and cancer. Cell and Bioscience, 3(1) Retrieved from www.scopus.com

Jalili, M., Pati, S., Rath, B., Bjørklund, G., & Singh, R. B. (2013). Effect of diet and nutrients on molecular mechanism of gene expression mediated by nuclear receptor and epigenetic modulation. Open Nutraceuticals Journal, 6(1), 27-34. Retrieved from www.scopus.com

Johnson, S. A., & Arjmandi, B. H. (2013). Evidence for anti-cancer properties of blueberries: A mini-review. Anti-Cancer Agents in Medicinal Chemistry, 13(8), 1142-1148. Retrieved from www.scopus.com

Kaliora, A. C., Kogiannou, D. A. A., Kefalas, P., Papassideri, I. S., & Kalogeropoulos, N. (2014). Phenolic profiles and antioxidant and anticarcinogenic activities of greek herbal infusions; balancing delight and chemoprevention? Food Chemistry, 142, 233-241. Retrieved from www.scopus.com

Khan, S. I., Aumsuwan, P., Khan, I. A., Walker, L. A., & Dasmahapatra, A. K. (2012). Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome. Chemical Research in Toxicology, 25(1), 61-73. Retrieved from www.scopus.com

Kim, S. O., & Kim, M. R. (2013). (-)-Epigallocatechin 3-gallate inhibits invasion by inducing the expression of raf kinase inhibitor protein in AsPC-1 human pancreatic adenocarcinoma cells through the modulation of histone deacetylase activity. International Journal of Oncology, 42(1), 349-358. Retrieved from www.scopus.com

Kitagawa, Y., Ohkura, N., & Sakaguchi, S. (2013). Molecular determinants of regulatory T cell development: The essential roles of epigenetic changes. Frontiers in Immunology, 4(MAY) Retrieved from www.scopus.com

Korkina, L. G., Pastore, S., Dellambra, E., & De Luca, C. (2013). New molecular and cellular targets for chemoprevention and treatment of skin tumors by plant polyphenols: A critical review. Current Medicinal Chemistry, 20(7), 852-868. Retrieved from www.scopus.com

Kumar, M., Nagpal, R., Verma, V., Kumar, A., Kaur, N., Hemalatha, R., . . . Singh, B. (2013). Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutrition Reviews, 71(1), 23-34. Retrieved from www.scopus.com

Küppers, R. (2012). New insights in the biology of hodgkin lymphoma. Hematology / the Education Program of the American Society of Hematology.American Society of Hematology.Education Program, 2012, 328-334. Retrieved from www.scopus.com

Latruffe, N., & Rifler, J. -. (2013). Bioactive polyphenols from grapes and wine emphasized with resveratrol. Current Pharmaceutical Design, 19(34), 6053-6063. Retrieved from www.scopus.com

Lecumberri, E., Dupertuis, Y. M., Miralbell, R., & Pichard, C. (2013). Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clinical Nutrition, 32(6), 894-903. Retrieved from www.scopus.com

Lee, J. H., Khor, T. O., Shu, L., Su, Z. -., Fuentes, F., & Kong, A. -. T. (2013). Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacology and Therapeutics, 137(2), 153-171. Retrieved fromwww.scopus.com

Leonard, S., Wei, W., Anderton, J., Vockerodt, M., Rowe, M., Murray, P. G., & Woodman, C. B. (2011). Epigenetic and transcriptional changes which follow epstein-barr virus infection of germinal center B cells and their relevance to the pathogenesis of hodgkin’s lymphoma. Journal of Virology, 85(18), 9568-9577. Retrieved from www.scopus.com

Leuschner, C., Enright, F. M., Melrose, P. A., & Hansel, W. (2001). Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells. Prostate, 46(2), 98-107. Retrieved from www.scopus.com

Lillycrop, K. A., & Burdge, G. C. (2012). Epigenetics of nutrition Retrieved from www.scopus.com

Mackenzie, G. G., Queisser, N., Wolfson, M. L., Fraga, C. G., Adamo, A. M., & Oteiza, P. I. (2008). Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-κB and STAT3 pathways in hodgkin’s lymphoma cells. International Journal of Cancer, 123(1), 56-65. Retrieved from www.scopus.com

Martin, M. A., Goya, L., & Ramos, S. (2013). Potential for preventive effects of cocoa and cocoa polyphenols in cancer. Food and Chemical Toxicology, 56, 336-351. Retrieved from www.scopus.com

Martin, S. L., Hardy, T. M., & Tollefsbol, T. O. (2013). Medicinal chemistry of the epigenetic diet and caloric restriction. Current Medicinal Chemistry, 20(32), 4050-4059. Retrieved from www.scopus.com

Meadows, G. G. (2012). Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes. Cancer and Metastasis Reviews, 31(3-4), 441-454. Retrieved from www.scopus.com

Medina-Franco, J. L., & Yoo, J. (2013). Molecular modeling and virtual screening of DNA methyltransferase inhibitors. Current Pharmaceutical Design, 19(12), 2138-2147. Retrieved from www.scopus.com

Meeran, S. M., Patel, S. N., Chan, T. -., & Tollefsbol, T. O. (2011). A novel prodrug of epigallocatechin-3-gallate: Differential epigenetic hTERT repression in human breast cancer cells. Cancer Prevention Research, 4(8), 1243-1254. Retrieved from www.scopus.com

Mendelsohn, A. R., & Larrick, J. W. (2013). The DNA methylome as a biomarker for epigenetic instability and human aging. Rejuvenation Research, 16(1), 74-77. Retrieved from www.scopus.com

Milagro, F. I., Mansego, M. L., De Miguel, C., & Martínez, J. A. (2013). Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives. Molecular Aspects of Medicine, 34(4), 782-812. Retrieved from www.scopus.com

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Mushtaq, M., & Wani, S. M. (2013). Polyphenols and human health- A review. International Journal of Pharma and Bio Sciences, 4(2), B338-B360. Retrieved from www.scopus.com

Neelakandan, K., Babu, P., & Nair, S. (2012). Emerging roles for modulation of microRNA signatures in cancer chemoprevention. Current Cancer Drug Targets, 12(6), 716-740. Retrieved from www.scopus.com

Ntziachristos, P., Mullenders, J., Trimarchi, T., & Aifantis, I. (2013). Mechanisms of epigenetic regulation of leukemia onset and progression Retrieved from www.scopus.com

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Papoutsis, A. J., Lamore, S. D., Wondrak, G. T., Selmin, O. I., & Romagnolo, D. F. (2010). Resveratrol prevents epigenetic silencing of BRCA-1 by the aromatic hydrocarbon receptor in human breast cancer cells. Journal of Nutrition, 140(9), 1607-1614. Retrieved from www.scopus.com

Pham, T. X., & Lee, J. (2012). Dietary regulation of histone acetylases and deacetylases for the prevention of metabolic diseases. Nutrients, 4(12), 1868-1886. Retrieved from www.scopus.com

Philippou, Y., Hadjipavlou, M., Khan, S., & Rane, A. (2013). Complementary and alternative medicine (CAM) in prostate and bladder cancer. BJU International, 112(8), 1073-1079. Retrieved from www.scopus.com

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Rakel, D. (2013). Superfood blend for localized prostate cancer. Integrative Medicine Alert, 16(9), 107-108. Retrieved from www.scopus.com

Reuter, S., Gupta, S. C., Park, B., Goel, A., & Aggarwal, B. B. (2011). Epigenetic changes induced by curcumin and other natural compounds. Genes and Nutrition, 6(2), 93-108. Retrieved from www.scopus.com

Salvador, L. A., & Luesch, H. (2012). Discovery and mechanism of natural products as modulators of histone acetylation. Current Drug Targets, 13(8), 1029-1047. Retrieved from www.scopus.com

Sangshetti, J. N., Sakle, N. S., Dehghan, M. H. G., & Shinde, D. B. (2013). Histone deacetylases as targets for multiple diseases. Mini-Reviews in Medicinal Chemistry, 13(7), 1005-1026. Retrieved from www.scopus.com

Shankar, S., Kumar, D., & Srivastava, R. K. (2013). Epigenetic modifications by dietary phytochemicals: Implications for personalized nutrition. Pharmacology and Therapeutics, 138(1), 1-17. Retrieved from www.scopus.com

Shirakami, Y., Shimizu, M., & Moriwaki, H. (2012). Cancer chemoprevention with green tea catechins: From bench to bed. Current Drug Targets, 13(14), 1842-1857. Retrieved from www.scopus.com

Shu, L., Khor, T. O., Lee, J. -., Boyanapalli, S. S. S., Huang, Y., Wu, T. -., . . . Kong, A. -. T. (2011). Epigenetic CpG demethylation of the promoter and reactivation of the expression of neurog1 by curcumin in prostate LNCaP cells. AAPS Journal, 13(4), 606-614. Retrieved from www.scopus.com

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