How PPs Fight Cancer

Home/About/Research/How PPs Fight Cancer
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.

Abusnina, A., Keravis, T., Yougbaré, I., Bronner, C., & Lugnier, C. (2011). Anti-proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1. Molecular Nutrition and Food Research, 55(11), 1677-1689. Retrieved from

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Min, N. Y., Kim, J. -., Choi, J. -., Liang, W., Ko, Y. J., Rhee, S., . . . Lee, K. -. (2012). Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate. Biochemical and Biophysical Research Communications, 421(1), 91-97. Retrieved

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

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

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

Ong, T. P., Moreno, F. S., & Ross, S. A. (2012). Targeting the epigenome with bioactive food components for cancer prevention. Journal of Nutrigenetics and Nutrigenomics, 4(5), 275-292. Retrieved from

Pan, M. -., Lai, C. -., Wu, J. -., & Ho, C. -. (2013). Epigenetic and disease targets by polyphenols. Current Pharmaceutical Design, 19(34), 6156-6185. Retrieved from

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

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

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

Poloni, A., Goteri, G., Zizzi, A., Serrani, F., Trappolini, S., Costantini, B., . . . Leoni, P. (2013). Prognostic role of immunohistochemical analysis of 5 mc in myelodysplastic syndromes. European Journal of Haematology, 91(3), 219-227. Retrieved from

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

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

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

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

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

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

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

Shukla, S., Khan, S., Tollefsbol, T. O., & Meeran, S. M. (2013). Genetics and epigenetics of lung cancer: Mechanisms and future perspectives. Current Cancer Therapy Reviews, 9(2), 97-110. Retrieved from

Singh, V., Sharma, P., & Capalash, N. (2013). DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer. Current Cancer Drug Targets, 13(4), 379-399. Retrieved from

Stefanska, B., Karlic, H., Varga, F., Fabianowska-Majewska, K., & Haslberger, A. G. (2012). Epigenetic mechanisms in anti-cancer actions of bioactive food components – the implications in cancer prevention. British Journal of Pharmacology, 167(2), 279-297. Retrieved from

Supic, G., Jagodic, M., & Magic, Z. (2013). Epigenetics: A new link between nutrition and cancer. Nutrition and Cancer, 65(6), 781-792. Retrieved from

Syed, D. N., Chamcheu, J. -., Adhami, V. M., & Mukhtar, H. (2013). Pomegranate extracts and cancer prevention: Molecular and cellular activities. Anti-Cancer Agents in Medicinal Chemistry, 13(8), 1149-1161. Retrieved from

Taylor, K. H., Briley, A., Wang, Z., Cheng, J., Shi, H., & Caldwell, C. W. (2013). Aberrant epigenetic gene regulation in lymphoid malignancies. Seminars in Hematology, 50(1), 38-47. Retrieved from

Teiten, M. -., Dicato, M., & Diederich, M. (2013). Curcumin as a regulator of epigenetic events. Molecular Nutrition and Food Research, 57(9), 1619-1629. Retrieved from

Vanden Berghe, W. (2012). Epigenetic impact of dietary polyphenols in cancer chemoprevention: Lifelong remodeling of our epigenomes. Pharmacological Research, 65(6), 565-576. Retrieved from

Verma, M. (2012). Cancer control and prevention by nutrition and epigenetic approaches. Antioxidants and Redox Signaling, 17(2), 355-364. Retrieved from

Verma, M. (2013). Cancer control and prevention: Nutrition and epigenetics. Current Opinion in Clinical Nutrition and Metabolic Care, 16(4), 376-384. Retrieved from

Ververis, K., Hiong, A., Karagiannis, T. C., & Licciardi, P. V. (2013). Histone deacetylase inhibitors (HDACIS): Multitargeted anticancer agents. Biologics: Targets and Therapy, 7(1), 47-60. Retrieved from

Vizoso, M., & Esteller, M. (2013). German-catalan workshop on epigenetics and cancer. Epigenetics, 8(9), 998-1003. Retrieved from

Wang, J., Wu, Z., Li, D., Li, N., Dindot, S. V., Satterfield, M. C., . . . Wu, G. (2012). Nutrition, epigenetics, and metabolic syndrome. Antioxidants and Redox Signaling, 17(2), 282-301. Retrieved from

Wang, S. -., Huang, M. -., Li, J. -., Lai, F. -., Lee, H. -., & Hsu, Y. -. (2013). Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells. Acta Pharmacologica Sinica, 34(11), 1411-1419. Retrieved from

Wang, Y., Li, Y., Liu, X., & Cho, W. C. S. (2013). Genetic and epigenetic studies for determining molecular targets of natural product anticancer agents. Current Cancer Drug Targets, 13(5), 506-518. Retrieved from

Wang, Z., Fan, J., Liu, M., Yeung, S., Chang, A., Chow, M. S., . . . Huang, Y. (2013). Nutraceuticals for prostate cancer chemoprevention: From molecular mechanisms to clinical application. Expert Opinion on Investigational Drugs, 22(12), 1613-1626. Retrieved from

Wang, Z., Li, L., Su, X., Gao, Z., Srivastava, G., Murray, P. G., . . . Tao, Q. (2012). Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-hodgkin and hodgkin lymphomas. Journal of Translational Medicine, 10(1) Retrieved from

Wong, C. P., Nguyen, L. P., Noh, S. K., Bray, T. M., Bruno, R. S., & Ho, E. (2011). Induction of regulatory T cells by green tea polyphenol EGCG. Immunology Letters, 139(1-2), 7-13. Retrieved from

Yu, A. F., Shen, J. Z., Chen, Z. Z., Fan, L. P., & Lin, F. A. (2008). [Demethylation and transcription of p16 gene in malignant lymphoma cell line CA46 induced by EGCG]. Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology, 16(5), 1073-1078. Retrieved from

Yuan, J. -. (2013). Cancer prevention by green tea: Evidence from epidemiologic studies 1-4. American Journal of Clinical Nutrition, 98(6), 1676S-1681S. Retrieved from

Zaidi, S. K., Van Wijnen, A. J., Lian, J. B., Stein, J. L., & Stein, G. S. (2013). Targeting deregulated epigenetic control in cancer. Journal of Cellular Physiology, 228(11), 2103-2108. Retrieved from

Zhang, W., Wang, J., & Ke, X. -. (2013). Research progress in the biology of hodgkin’s lymphoma in the 54th ASH annual meeting. Journal of Leukemia and Lymphoma, 22(7), 385-386. Retrieved from