Complementary and alternative medicines in prostate cancer: from bench to bedside?

Complementary and alternative medicine (CAM) use is common among adults, and recent reports suggest that 25%-50% of prostate cancer (PCa) patients use at least one CAM modality. The most common CAM modalities used by PCa patients are vitamin and herbal preparations with purported antitumor effects despite only modest underlying preclinical or clinical evidence of efficacy. In this review we provide a brief overview of the basic scientific and clinical studies underlying the most common herbal and vitamin preparations including common antioxidants, pomegranate extract, green tea, turmeric, resveratrol, silibinin, and herbal combination preparations. When available, prostate cancer clinical trial data are reviewed. Importantly, we have compared the concentration of these agents used in in vitro experiments to that likely to be achievable in humans. From the available data we conclude that there is insufficient evidence to support the use of CAMs for the treatment of prostate cancer patients outside of a clinical trial. The purpose of this review is to more rigorously evaluate CAM therapy in prostate cancer and educate oncologists and patients. This review focuses on examples from the general classes of agents in common use.

[1]  B. Aggarwal,et al.  Zyflamend suppresses growth and sensitizes human pancreatic tumors to gemcitabine in an orthotopic mouse model through modulation of multiple targets , 2012, International journal of cancer.

[2]  H. Ke,et al.  Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases , 2012, Cell.

[3]  J. Capodice,et al.  Zyflamend inhibits the expression and function of androgen receptor and acts synergistically with bicalutimide to inhibit prostate cancer cell growth , 2012, The Prostate.

[4]  C. Lawton,et al.  Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) , 2012 .

[5]  K. Wellington,et al.  Silymarin: A Review of its Clinical Properties in the Management of Hepatic Disorders , 2012, BioDrugs.

[6]  S. Baek,et al.  Zyflamend Reduces the Expression of Androgen Receptor in a Model of Castrate-Resistant Prostate Cancer , 2011, Nutrition and cancer.

[7]  X. Shu,et al.  Green tea consumption and colorectal cancer risk: a report from the Shanghai Men's Health Study. , 2011, Carcinogenesis.

[8]  R. Bristow,et al.  Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways , 2011, Radiation oncology.

[9]  Jeremy J. W. Chen,et al.  Curcumin Induces EGFR Degradation in Lung Adenocarcinoma and Modulates p38 Activation in Intestine: The Versatile Adjuvant for Gefitinib Therapy , 2011, PloS one.

[10]  M. Stearns,et al.  Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors. , 2011, Translational oncology.

[11]  I. Ramzan,et al.  Molecular Pathways for Cancer Chemoprevention by Dietary Phytochemicals , 2011, Nutrition and cancer.

[12]  V. Adhami,et al.  Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  T. Walle.  Bioavailability of resveratrol , 2011, Annals of the New York Academy of Sciences.

[14]  T. Chiba,et al.  Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers , 2011, Cancer Chemotherapy and Pharmacology.

[15]  S. Shankar,et al.  Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells , 2010, PloS one.

[16]  L. Subramanian,et al.  Resveratrol: Challenges in Translation to the Clinic — A Critical Discussion , 2010, Clinical Cancer Research.

[17]  W. Cheng,et al.  Selenium Compounds Activate ATM-dependent DNA Damage Response via the Mismatch Repair Protein hMLH1 in Colorectal Cancer Cells* , 2010, The Journal of Biological Chemistry.

[18]  M. Lucia,et al.  A study of high‐dose oral silybin‐phytosome followed by prostatectomy in patients with localized prostate cancer , 2010, The Prostate.

[19]  Zhiwei Wang,et al.  Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. , 2010, Cancer research.

[20]  S. Ramsey,et al.  Complementary and alternative medicine use among newly diagnosed prostate cancer patients , 2010, Supportive Care in Cancer.

[21]  H. Hua,et al.  (-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma , 2010, Breast Cancer Research.

[22]  Jun Tian,et al.  Repressive Effects of Resveratrol on Androgen Receptor Transcriptional Activity , 2009, PloS one.

[23]  Barbara Bloom,et al.  Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. , 2009, National health statistics reports.

[24]  J. Crowley,et al.  Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). , 2009, JAMA.

[25]  P. Barnes,et al.  Complementary and alternative medicine use among adults and children: United States, 2007. , 2008, National health statistics reports.

[26]  François G. Meyer,et al.  Insulin-like Growth Factors, Their Binding Proteins, and Prostate Cancer Risk: Analysis of Individual Patient Data from 12 Prospective Studies , 2008, Annals of Internal Medicine.

[27]  G. Bubley,et al.  Prostasol and venous thromboembolism. , 2008, Urology.

[28]  N. Seeram,et al.  Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-κB-dependent mechanism , 2008, Molecular Cancer Therapeutics.

[29]  A. Kong,et al.  Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism , 2008, Molecular Cancer Therapeutics.

[30]  B. Aggarwal,et al.  Curcumin and cancer: an "old-age" disease with an "age-old" solution. , 2008, Cancer letters.

[31]  M. Suchard,et al.  Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects. , 2008, Journal of medicinal food.

[32]  B. Haendler,et al.  Androgen receptor acetylation sites differentially regulate gene control , 2008, Journal of cellular biochemistry.

[33]  S. Srivastava,et al.  Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome. , 2008, Cancer biology & therapy.

[34]  V. Adhami,et al.  Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis , 2008, Oncogene.

[35]  H. Inui,et al.  Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells. , 2007, Journal of nutritional science and vitaminology.

[36]  Jeffrey E. Green,et al.  Inhibition of prostate cancer growth by muscadine grape skin extract and resveratrol through distinct mechanisms. , 2007, Cancer research.

[37]  E. Pozo-Guisado,et al.  Non-genomic action of resveratrol on androgen and oestrogen receptors in prostate cancer: modulation of the phosphoinositide 3-kinase pathway , 2007, British Journal of Cancer.

[38]  B. Aggarwal,et al.  Zyflamend, a Polyherbal Preparation, Inhibits Invasion, Suppresses Osteoclastogenesis, and Potentiates Apoptosis Through Down-Regulation of NF-κ B Activation and NF-κ B–Regulated Gene Products , 2007 .

[39]  R. Agarwal,et al.  Silibinin synergizes with mitoxantrone to inhibit cell growth and induce apoptosis in human prostate cancer cells , 2007, International journal of cancer.

[40]  B. Aggarwal,et al.  Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. , 2007, Cancer research.

[41]  V. Adhami,et al.  Combined Inhibitory Effects of Green Tea Polyphenols and Selective Cyclooxygenase-2 Inhibitors on the Growth of Human Prostate Cancer Cells Both In vitro and In vivo , 2007, Clinical Cancer Research.

[42]  B. Aggarwal,et al.  Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-κB and nuclear factor-κB–regulated gene products in IFN-α–sensitive and IFN-α–resistant human bladder cancer cells , 2007, Molecular Cancer Therapeutics.

[43]  Hui Wang,et al.  Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. , 2007, Cancer research.

[44]  P. Fernández-Salguero,et al.  Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. , 2006, Journal of andrology.

[45]  B. Aggarwal,et al.  Curcumin: the Indian solid gold. , 2007, Advances in experimental medicine and biology.

[46]  N. Munshi,et al.  Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. , 2006, Blood.

[47]  David Heber,et al.  Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. , 2006, The Journal of nutrition.

[48]  Shinichi Kuriyama,et al.  Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. , 2006, JAMA.

[49]  N. Pattabiraman,et al.  Hormonal Control of Androgen Receptor Function through SIRT1 , 2006, Molecular and Cellular Biology.

[50]  Shile Huang,et al.  Curcumin inhibits the mammalian target of rapamycin‐mediated signaling pathways in cancer cells , 2006, International journal of cancer.

[51]  R. Elashoff,et al.  Phase II Study of Pomegranate Juice for Men with Rising Prostate-Specific Antigen following Surgery or Radiation for Prostate Cancer , 2006, Clinical Cancer Research.

[52]  A. Dennison,et al.  Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences , 2006, Clinical Cancer Research.

[53]  Giovanni Castagnetti,et al.  Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. , 2006, Cancer research.

[54]  C. Dabrosin,et al.  Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. , 2006, Cancer letters.

[55]  J. Tchinda,et al.  Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. , 2006, Science.

[56]  V. Adhami,et al.  Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[57]  E. Campo,et al.  Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse , 2005, British Journal of Cancer.

[58]  R. Buttyan,et al.  Zyflamend®, a Unique Herbal Preparation With Nonselective OX Inhibitory Activity, Induces Apoptosis of Prostate Cancer Cells That Lack COX-2 Expression , 2005, Nutrition and cancer.

[59]  D. Alberts,et al.  Effects of Dosing Condition on the Oral Bioavailability of Green Tea Catechins after Single-Dose Administration of Polyphenon E in Healthy Individuals , 2005, Clinical Cancer Research.

[60]  L. Kopelovich,et al.  (−)-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 , 2005, Clinical Cancer Research.

[61]  J. Thrasher,et al.  Small-interfering RNA–induced androgen receptor silencing leads to apoptotic cell death in prostate cancer , 2005, Molecular Cancer Therapeutics.

[62]  D. Karunagaran,et al.  Sensitization of Taxol-induced Apoptosis by Curcumin Involves Down-regulation of Nuclear Factor-κB and the Serine/Threonine Kinase Akt and Is Independent of Tubulin Polymerization* , 2005, Journal of Biological Chemistry.

[63]  Michael M Lieber,et al.  Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). , 2005, Journal of the National Cancer Institute.

[64]  Fred Saad,et al.  Nuclear Factor-κB Nuclear Localization Is Predictive of Biochemical Recurrence in Patients with Positive Margin Prostate Cancer , 2004, Clinical Cancer Research.

[65]  T. Walle,et al.  HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS , 2004, Drug Metabolism and Disposition.

[66]  P. Kantoff,et al.  Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  M. Evans,et al.  Oxidative DNA damage and disease: induction, repair and significance. , 2004, Mutation research.

[68]  G. Combs,et al.  Status of selenium in prostate cancer prevention , 2004, British Journal of Cancer.

[69]  Zhengxin Wang,et al.  Modulation of androgen receptor‐dependent transcription by resveratrol and genistein in prostate cancer cells , 2004, The Prostate.

[70]  Hsin-Yi Huang,et al.  Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats , 2004, Clinical Cancer Research.

[71]  A. Costello,et al.  Inorganic selenium retards progression of experimental hormone refractory prostate cancer. , 2004, The Journal of urology.

[72]  C. Ip,et al.  Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. , 2003, Cancer research.

[73]  D. Alberts,et al.  Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[74]  H. Mukhtar,et al.  Role of p53 and NF-κB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells , 2003, Oncogene.

[75]  M. Evans,et al.  Oxidative DNA damage: mechanisms, mutation, and disease , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[76]  P. Novotny,et al.  A Phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma , 2003, Cancer.

[77]  R. Longtin.  The pomegranate: nature's power fruit? , 2003, Journal of the National Cancer Institute.

[78]  Insu P. Lee,et al.  A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression. , 2003, DNA and cell biology.

[79]  Z. Dong,et al.  Signal transduction pathways: targets for green and black tea polyphenols. , 2003, Journal of biochemistry and molecular biology.

[80]  D. Goldberg,et al.  Absorption of three wine-related polyphenols in three different matrices by healthy subjects. , 2003, Clinical biochemistry.

[81]  Sanjeev Banerjee,et al.  Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation , 2002, Oncogene.

[82]  R. Agarwal,et al.  Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[83]  L. Klotz,et al.  Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. , 2002, The Journal of urology.

[84]  R. Agarwal,et al.  Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. , 2002, Cancer research.

[85]  Chao-yuan Huang,et al.  Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBPβ expressions and suppressing NF‐κB activation , 2002, The Prostate.

[86]  M. Menon,et al.  Resveratrol induces prostate cancer cell entry into s phase and inhibits DNA synthesis. , 2002, Cancer research.

[87]  B. Aggarwal,et al.  Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines , 2001, Oncogene.

[88]  J. Jacobson,et al.  Complementary and alternative medicine in prostate cancer , 2001, Current oncology reports.

[89]  S. Jee,et al.  Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. , 2001, Anticancer research.

[90]  Y. Kimura,et al.  Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. , 2001, Journal of NutriLife.

[91]  F. Khuri,et al.  Phase I trial of oral green tea extract in adult patients with solid tumors. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[92]  J. Neuzil,et al.  Selective cancer cell killing by α-tocopheryl succinate , 2001, British Journal of Cancer.

[93]  J. Manola,et al.  Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. , 2001, Urology.

[94]  D. Alberts,et al.  Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[95]  E. Riboli,et al.  Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. , 2000, Journal of the National Cancer Institute.

[96]  P. Langley.  Why a pomegranate? , 2000, BMJ : British Medical Journal.

[97]  R. Agarwal,et al.  Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells. , 2000, Cancer research.

[98]  A. Shabsigh,et al.  Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. , 2000, Journal of Urology.

[99]  F. Tomás-Barberán,et al.  Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. , 2000, Journal of agricultural and food chemistry.

[100]  P. Cohen,et al.  Role of insulin‐like growth factors and their binding proteins in growth control and carcinogenesis , 2000, Journal of cellular physiology.

[101]  S. Gupta,et al.  Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. , 2000, Toxicology and applied pharmacology.

[102]  J. Epstein,et al.  Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. , 1999, The American journal of pathology.

[103]  J. Lin,et al.  Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. , 1999, Biochemical pharmacology.

[104]  F. Saint,et al.  High-grade inflammation in prostate cancer as a prognostic factor for biochemical recurrence after radical prostatectomy. Pathologist Multi Center Study Group. , 1999, Urology.

[105]  H. Ganther,et al.  Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. , 1999, Carcinogenesis.

[106]  J. Trachtenberg,et al.  Prevalence and patterns of the use of complementary therapies among prostate cancer patients: an epidemiological analysis. , 1999, The Journal of urology.

[107]  R. Tiwari,et al.  Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. , 1999, International journal of oncology.

[108]  Yihai Cao,et al.  Angiogenesis inhibited by drinking tea , 1999, Nature.

[109]  Cme Article.  HIGH-GRADE INFLAMMATION IN PROSTATE CANCER AS A PROGNOSTIC FACTOR FOR BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY , 1999 .

[110]  T. Hurley,et al.  Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. , 1998, Journal of the National Cancer Institute.

[111]  G. Yang,et al.  Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. , 1998, Carcinogenesis.

[112]  S. Hirota,et al.  Modulation of cancer chemotherapy by green tea. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[113]  Chung S. Yang.  Inhibition of carcinogenesis by tea , 1997, Nature.

[114]  Z. Darżynkiewicz,et al.  Apoptosis and cell cycle effects induced by extracts of the Chinese herbal preparation PC SPES. , 1997, International journal of oncology.

[115]  E. Skrzypczak‐Jankun,et al.  Why drinking green tea could prevent cancer , 1997, Nature.

[116]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[117]  H. Mukhtar,et al.  Tea in chemoprevention of cancer. , 1996, International journal of oncology.

[118]  G. Kuttan,et al.  Anti-tumour and antioxidant activity of natural curcuminoids. , 1995, Cancer letters.

[119]  Z. Y. Wang,et al.  Tea and cancer. , 1993, Journal of the National Cancer Institute.

[120]  H N Graham,et al.  Green tea composition, consumption, and polyphenol chemistry. , 1992, Preventive medicine.

[121]  L. Rosenberg.  Coffee and tea consumption in relation to the risk of large bowel cancer: a review of epidemiologic studies. , 1990, Cancer letters.

[122]  G. Labbe,et al.  Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. , 1990, Biochemical pharmacology.

[123]  B. Schneider,et al.  Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. , 1989, Journal of hepatology.

[124]  K. McPherson,et al.  A case-control study , 2007 .

[125]  Y. Oshika,et al.  P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo. , 1996, British Journal of Cancer.