Life Extension Magazine December 2013

Report

New Study Reveals Four Nutrients that Lower PSA and Slow Cancer Progression

By Ramon Gonzales

New Study Reveals Four Nutrients that Lower PSA and Slow Cancer Progression

Prostate cancer is a leading cause of cancer death among men. Yet, only about 15% of new prostate cancer diagnoses require immediate and aggressive treatment.1,2

The majority of newly diagnosed prostate cancer cases have low- or intermediate-risk malignancies. For men with low risk malignancies, oncologists sometimes practice “watchful waiting” or “active surveillance,” monitoring parameters such as prostate-specific antigen (PSA) to evaluate tumor progression.3,4 This approach can delay the need for aggressive treatment, and in many cases is turning out to reduce or eliminate the need for surgery, chemo, or radiation therapy.3

During this period of watchful waiting, there is an additional option that has been shown to lower PSA. A landmark study from the United Kingdom has demonstrated that a combination of four foods—a fruit (pomegranate), an herb (green tea), a spice (turmeric), and a vegetable (broccoli)—concentrated into a pill, dramatically slowed markers of prostate cancer growth by a median of nearly 64%.5

Working closely with the National Cancer Research Network, this formula was developed based on extensive documentation showing how certain foods function to slow prostate cancer growth. We begin this report with a critical review of this groundbreaking study conducted on human prostate cancer patients.

Why PSA Matters in Prostate Cancer

PSA and PSA kinetics are the primary markers to follow disease progress in men with known cancer of the prostate gland.83,84 But PSA is more than just a marker; we now realize that it is an enzyme that degrades the matrix proteins holding cells together.28 That is one way the cancer invades and spreads.

A tumor that produces a rapidly rising PSA, therefore, is one at risk for breaking out of the prostate gland itself and spreading either into local tissue or forming distant metastases, both of which place the patient at high risk of death.85

That’s why physicians and patients should follow PSA levels carefully once a prostate tumor has been discovered. And that’s why therapies that lower PSA are not just producing an encouraging marker, they are in fact demonstrably slowing disease progression and lowering the patient’s risk of dying.

Landmark UK Study: Food Pill Slows Evidence of Prostate Cancer Growth

Landmark UK Study: Food Pill Slows Evidence of Prostate Cancer Growth  

In June of 2013, the American Society of Clinical Oncology included in its program a report on a “food pill” that had a dramatic impact on men with prostate cancer.5 For those who don’t know, the annual conference of the American Society of Clinical Oncology (ASCO) is where many cancer treatment breakthroughs are announced to the world.

The study reported at the ASCO conference was an exploration of the role of four polyphenol-rich foods with known anti-cancer properties.5 The trial development team worked in partnership with the UK government’s National Cancer Research Network, which ensured the highest scientific credibility and quality assurance. They extensively scrutinized the clinical and laboratory data for foods that have a high chance of an anti-cancer effect. They came up with a specific blend of four cancer-fighting foods concentrated into a capsule designed to be taken twice daily. They then set out to test its effect in the most rigorous of scientific trials—a double-blind placebo-controlled randomized trial within which they examined its effect on prostate-specific antigen, or PSA.

The researchers recruited 203 men aged 53 to 89 years (average age 74 years) with prostate cancer proven by biopsy.5 Fifty-nine percent of the men had not yet undergone any treatment and were being followed closely with periodic PSA measurements, while 41% had already had a radical intervention (surgery, chemotherapy, or radiation) but had relapsed with climbing PSA levels.

The subjects were then randomly assigned to receive either a twice-daily oral capsule containing a blend of pomegranate seed, green tea, turmeric, and broccoli, or an identical placebo for 6 months. At baseline, there were no significant differences between the two groups, except that the placebo group was on average 4 years older than the treatment group. Neither the doctors supervising the trial nor the men knew whether they were taking a placebo or the test product.

The men in the study had their PSA levels measured at baseline, at 3 months, and at 6 months, to determine the rate of rise. The results were remarkable.

In the placebo group, PSA levels rose by a median of 78.5% over the 6-month period, while in the supplemented group, PSA rose by a median of only 14.7%, a statistically significant 63.8% difference.5

In addition, and importantly, 46% of men in the supplemented group had a stable or lower PSA by the end of the study, compared with just 14% of the placebo group; again, this was a significant difference, and suggested that in nearly half of the treated men, their cancers had stopped growing or had even regressed.

In another remarkable measure, just 7.4% of supplemented men being monitored by active surveillance or watchful waiting required a change in management plan, while 26% of those in the placebo group required a change in their management plan.5 In other words, the supplement directly supported the decision to defer care and avoid painful, costly, and invasive procedures in this group of men.

Following the success of this trial, the research team is designing a range of new scientific trials involving this unique fruit and vegetable blend collaborating with academic cancer centers across the world. These include men already taking androgen deprivation therapies, or those in PSA remission following successful primary treatments such as surgery, brachytherapy, or radiotherapy. They are also partnering with clinicians outside the urology cancer field to determine its effect on osteoarthritis, chronic breast pain, hot flushes, and even tinnitus, and hopefully the results of these trials will be available by early 2015.

Let’s now look more closely at each of the ingredients in this new prostate-cancer-fighting food pill, to see what each one brings uniquely to the formula and how each reinforces the other to reduce the risk of prostate cancer progression.

What You Need to Know
Functional Foods as Powerful Combatants Against Prostate Cancer

Functional Foods as Powerful Combatants Against Prostate Cancer

  • Prostate cancer becomes a killer when it invades or metastasizes; prior to those events it can be detected and successfully treated.
  • But too many men with prostate cancer undergo needless and invasive surgery, chemo-, or radiation therapy.
  • A new pill containing concentrated forms of four functional foods has now been shown to significantly slow the rise of PSA, the major marker of prostate cancer progression.
  • The components, pomegranate, green tea, turmeric, and broccoli, have all independently been shown to have protective effects on prostate tissue; a new study demonstrates that they can work together in concert to slow the disease in men who already have prostate cancer.
  • Each food component works by different, but powerful, epigenetic mechanisms to modify the way prostate cells regulate their growth and development.
  • Using all four in one simple pill optimizes both prevention and treatment of prostate cancer, without significant side effects.

Life Extension Magazine December 2013

Report

New Study Reveals Four Nutrients that Lower PSA and Slow Cancer Progression

By Ramon Gonzales

Pomegranate

Pomegranate  

Pomegranate compounds suppress enzymes in the intestine and liver that convert certain molecules (procarcinogens) into cancer-causing agents.6,7 As it relates to those with prostate cancer, the active constituents in pomegranate have proven to be potent inducers of malignant cell death through apoptosis.8-16

During the development of androgen independence, prostate cancer cells are known to increase testosterone synthesis inside their own cells, which maintains cancer cell growth in the absence of significant amounts of circulating testosterone. Overexpression of the androgen receptor occurs in androgen-independent prostate cancer and has been proposed as another mechanism promoting the development of androgen independence. Pomegranate has been shown to inhibit expression of the androgen receptor and androgen synthesizing genes in prostate cells, which helps block an important survival mechanism utilized by prostate cancer cells to escape eradication.17

Multiple basic laboratory and human studies have demonstrated that pomegranate treatment, specifically various active compounds, slows PSA doubling time and reduces production of PSA in malignant prostate cells.12,14,18,19

In one recent study, pomegranate juice treatment in men with rising PSA after surgery or radiotherapy resulted in a significant delay in PSA doubling time (the time it takes PSA levels to rise) from a mean of 15 months before treatment to 54 months following supplementation.14 Another study found more modest, but still significant delay in doubling time, from 11.9 months to 18.8 months.18

Animal studies demonstrate additional anti-cancer activity in pomegranates. In a specialized mouse model of prostate cancer, 100% of untreated mice developed palpable tumors within 20 weeks, compared to as low as 20% in the group treated with pomegranate extract; the treated animals lived for up to a median of 92 weeks, more than twice as long as the 43 weeks survived by untreated mice.20

These remarkable results are observed in part because naturally occurring pomegranate polyphenols are concentrated in prostate tissue, facilitating their protective effects.19 Once in the prostate, these polyphenols selectively inhibit cancer cell proliferation, leaving healthy prostate tissue relatively unaffected.9,17 This is a potential “epigenetic” effect: pomegranate polyphenols decrease the expression of proteins that cancer cells use to support their rapid rate of replication.11,15,16, 21

Added prostate cancer-fighting benefits of pomegranate include reduction of the inflammation that drives cancer progression, suppression of new blood vessel growth within a forming prostate tumor, and increased expression of genes that keep cells clumped together normally, thereby inhibiting the invasive potential of prostate cancer.13,22-24

Green Tea

Green Tea

Green tea makes a unique contribution to the prostate-cancer-fighting pill as a result of a special combination of naturally occurring polyphenols called catechins.25-28

Studies show that one of green tea’s catechins, EGCG, accumulates specifically in prostate tissue, where it selectively kills cancer cells (leaving healthy cells unaffected) and reduces serum PSA levels.29-34

In a further demonstration of the cancer-suppressing role of green tea, when researchers studied men with a pre-cancerous condition called prostate intraepithelial neoplasia, they found only one tumor after one year in the 30 men given green tea polyphenols, while the 30 placebo recipients developed nine cancers.30 The treatment was safe, and as an extra bonus was found to reduce other lower urinary tract symptoms as well.

Green tea is already acknowledged as a cancer preventive in Japan because of epidemiological studies documenting prostate cancer risk reduction of up to 86% in men who drink the most green tea.31,35-37

Laboratory studies point to still other anti-cancer effects from green tea. Its components reduce genetic expression and activity of androgen receptors that most prostate cancers need to survive.34,38-40 Green tea also induces human cancer cell death by apoptosis through a variety of epigenetic mechanisms.24,41,42 And recent studies reveal polyphenols in brewed green tea shut off new blood vessel growth, important in slowing cancer development.26

Turmeric

Turmeric  

Turmeric’s unique contribution to the prostate-cancer-fighting pill is its extraordinary anti-inflammatory properties, provided chiefly by its natural primary component, curcumin.43,44 Reducing inflammation with curcumin reduces the metastases that ultimately kill prostate cancer patients.45-48 Curcumin also down-regulates genes involved in adhesion, motility, and invasiveness that prostate cancer cells need to invade and spread.49

Curcumin specifically inhibits prostate cancer cell production of PSA by blocking its genetic expression.50,51 At the same time, it also reduces activation of the androgen receptors on cancer cells that trigger increased production of PSA.52,53

But the whole turmeric root also contains important oils and other substances that enhance curcumin’s absorption and have health benefits of their own, including anti-cancer actions.54

Turmeric’s components also inhibit cancer cell proliferation, restore cancer cells’ ability to die normally by apoptosis, and decrease the density of blood vessels needed for tumor expansion.43 By modulating cell signaling mechanisms, curcumin arrests the out-of-control cell replication cycle typical in cancer.55,56

Curcumin also sensitizes cancer cells to chemo- and radiation therapy, as well as to the intrinsic “death factor” called TRAIL (TNF-related apoptosis-inducing ligand), one of the body’s natural cancer-suppressing mechanisms.57-59 Remarkably, these sensitizing effects are not found on normal, healthy cells, so they remain protected during treatment.59

The compound has also been found to block growth factors and androgen receptors used by cancer cells to support themselves.60-62

Broccoli

Broccoli

Broccoli’s unique contribution to the prostate-cancer-fighting pill is its ability to up-regulate phase II detoxifying enzymes in gut and liver tissue, enabling the body to render harmless thousands of potentially carcinogenic molecules in our diet.63-66 In addition, the naturally occurring sulfur-rich broccoli constituents sulforaphane, indole-3-carbinol (I3C), and others have now been identified as potent epigenetic regulators.63,67-69

These broccoli compounds control enzymes called histone deacetylases (HDAC) that regulate the genes encoded in DNA—including those responsible for promoting or suppressing cancer formation.63,67-69 Known collectively as histone deacetylase (HDAC) inhibitors, such molecules are prime objectives of Big Pharma.70,71

Men with high consumption of broccoli and other cruciferous vegetables have a 40% lower risk of invasive prostate cancer.72 And in animal studies, broccoli feeding reduced prostate tumor weight by 42% in prostate cancer-prone mice and suppressed growth of implanted human prostate cancer cells by 40%.68,73

Broccoli compounds reduce PSA production as a result of slowing prostate cancer cell replication in laboratory cell culture models.74-76 They appear to inhibit expression of the androgen receptors that prostate cancer needs to survive.75

Broccoli’s other prostate cancer-fighting properties include inhibition of growth and transcription factors that are activated in malignancies, restoration of normal tumor suppressor genes, and increased production of apoptosis-inducing proteins.77-82

Summary

Prostate cancer is a paradox: Its typically slow growth rate makes it possible to treat if discovered early, but once it has metastasized, it is often lethal.

The combination of four widely-recognized cancer-fighting foods, pomegranate, green tea, turmeric, and broccoli, in a single twice-daily pill has now been shown to significantly reduce the rate of rise of PSA, the tumor marker that indicates progression and invasion of prostate cancer.5

This new pill appears to work by providing cancer-suppressing actions at a wide variety of targets. All of this pill’s components have the capacity to cause favorable epigenetic changes, reversing the gene damage that leads to cancer development and restoring normal cancer suppression mechanisms.11,15,16,25,41,42,49,63,67-69

In a tightly controlled clinical trial, putting them together in a single pill was shown to be effective at slowing the growth of existing prostate cancers and preventing surgical and other side effect-prone procedures.

If you or someone you know suffers from prostate cancer, or is interested in preventing it, this new functional food pill, or its individual constituents, should be part of their daily program.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

Life Extension Magazine December 2013

Report

New Study Reveals Four Nutrients that Lower PSA and Slow Cancer Progression

By Ramon Gonzales

References

  1. Bastian PJ, Boorjian SA, Bossi A, et al. High-risk prostate cancer: from definition to contemporary management. Eur Urol. 2012 Jun;61(6):1096-106.
  2. Available at: http://www.cdc.gov/cancer/prostate/statistics/. Accessed September 17, 2013.
  3. Loeb S, Berglund A, Stattin P. Population based study of use and determinants of active surveillance and watchful waiting for low and intermediate risk prostate cancer. J Urol. 2013 May 30.
  4. Bul M, van den Bergh RC, Zhu X, et al. Outcomes of initially expectantly managed patients with low or intermediate risk screen-detected localized prostate cancer. BJU Int. 2012 Dec;110(11):1672-7.
  5. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. Summary of the National Cancer Research Network double-blind placebo controlled randomised trial. J Clin Oncol. 2013;31(Suppl; abs 5008).
  6. Faria A, Monteiro R, Azevedo I, Calhau C. Pomegranate juice effects on cytochrome P450S expression: in vivo studies. J Med Food. 2007 Dec;10(4):643-9.
  7. Saruwatari A, Okamura S, Nakajima Y, Narukawa Y, Takeda T, Tamura H. Pomegranate juice inhibits sulfoconjugation in Caco-2 human colon carcinoma cells. J Med Food. 2008 Dec;11(4):623-8.
  8. Vicinanza R, Zhang Y, Henning SM, Heber D. Pomegranate juice metabolites, ellagic acid and urolithin A, synergistically inhibit androgen-independent prostate cancer cell growth via distinct effects on cell cycle control and apoptosis. Evid Based Complement Alternat Med. 2013;2013:247504.
  9. Sineh Sepehr K, Baradaran B, Mazandarani M, Khori V, Shahneh FZ. Studies on the cytotoxic activities of Punica granatum L. var. spinosa (apple punice) extract on prostate cell line by induction of apoptosis. ISRN Pharm. 2012;2012:547942.
  10. Lee ST, Wu YL, Chien LH, Chen ST, Tzeng YK, Wu TF. Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell. Proteomics. 2012 Nov;12(21):3251-62.
  11. Gasmi J, Sanderson JT. Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells. J Agric Food Chem. 2010 Nov 10.
  12. Adhami VM, Khan N, Mukhtar H. Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer. 2009;61(6):811-5.
  13. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006 Jul 1;12(13):4018-26.
  14. Malik A, Mukhtar H. Prostate cancer prevention through pomegranate fruit. Cell Cycle. 2006 Feb;5(4):371-3.
  15. Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14813-8.
  16. Albrecht M, Jiang W, Kumi-Diaka J, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004 Fall;7(3):274-83.
  17. Hong MY, Seeram NP, Heber D. Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. J Nutr Biochem. 2008 Dec;19(12):848-55.
  18. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013 Mar;16(1):50-5.
  19. Seeram NP, Aronson WJ, Zhang Y, et al. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem. 2007 Sep 19;55(19):7732-7.
  20. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model. Carcinogenesis. 2012 Mar;33(3):644-51.
  21. Selvi BR, Batta K, Kishore AH, et al. Identification of a novel inhibitor of coactivator-associated arginine methyltransferase 1 (CARM1)-mediated methylation of histone H3 Arg-17. J Biol Chem. 2010 Mar 5;285(10):7143-52.
  22. Sartippour MR, Seeram NP, Rao JY, et al. Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. Int J Oncol. 2008 Feb;32(2):475-80.
  23. Wang L, Ho J, Glackin C, Martins-Green M. Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis. Transl Oncol. 2012 Oct;5(5):344-55.
  24. Pitchakarn P, Chewonarin T, Ogawa K, et al. Ellagic Acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac J Cancer Prev. 2013;14(5):2859-63.
  25. Connors SK, Chornokur G, Kumar NB. New insights into the mechanisms of green tea catechins in the chemoprevention of prostate cancer. Nutr Cancer. 2012;64(1):4-22.
  26. McCarthy S, Caporali A, Enkemann S, et al. Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer. Mol Oncol. 2007 Sep;1(2):196-204.
  27. O’Sullivan J, Sheridan J, Mulcahy H, Tenniswood M, Morrissey C. The effect of green tea on oxidative damage and tumour formation in Lobund-Wistar rats. Eur J Cancer Prev. 2008 Nov;17(6):489-501.
  28. Pezzato E, Sartor L, Dell’Aica I, et al. Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (-)epigallocatechin-3-gallate. Int J Cancer. 2004 Dec 10;112(5):787-92.
  29. Henning SM, Aronson W, Niu Y, et al. Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. J Nutr. 2006 Jul;136(7): 1839-43.
  30. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. 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. Cancer Res. 2006 Jan 15;66(2):1234-40.
  31. Pandey M, Gupta S. Green tea and prostate cancer: from bench to clinic. Front Biosci (Elite Ed). 2009;1:13-25.
  32. McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila). 2009 Jul;2(7):673-82.
  33. Siddiqui IA, Zaman N, Aziz MH, et al. Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis. 2006 Apr;27(4):833-9.
  34. Chuu CP, Chen RY, Kokontis JM, Hiipakka RA, Liao S. Suppression of androgen receptor signaling and prostate specific antigen expression by (-)-epigallocatechin-3-gallate in different progression stages of LNCaP prostate cancer cells. Cancer Lett. 2009 Mar 8;275(1):86-92.
  35. Fujiki H, Suganuma M. Green tea: an effective synergist with anticancer drugs for tertiary cancer prevention. Cancer Lett. 2012 Nov 28;324(2):119-25.
  36. Jian L, Lee AH, Binns CW. Tea and lycopene protect against prostate cancer. Asia Pac J Clin Nutr. 2007;16 Suppl 1:453-7.
  37. Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008 Jan 1;167(1):71-7.
  38. Harper CE, Patel BB, Wang J, Eltoum IA, Lamartiniere CA. Epigallocatechin-3-Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: mechanisms of action. Prostate. 2007 Oct 1;67(14):1576-89.
  39. Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. Faseb j. 2011 Apr;25(4):1198-207.
  40. Lee YH, Kwak J, Choi HK, et al. EGCG suppresses prostate cancer cell growth modulating acetylation of androgen receptor by anti-histone acetyltransferase activity. Int J Mol Med. 2012 Jul;30(1):69-74.
  41. Gupta K, Thakur VS, Bhaskaran N, et al. Green tea polyphenols induce p53-dependent and p53-independent apoptosis in prostate cancer cells through two distinct mechanisms. PLoS One. 2012;7(12):e52572.
  42. Hagen RM, Chedea VS, Mintoff CP, Bowler E, Morse HR, Ladomery MR. Epigallocatechin-3-gallate promotes apoptosis and expression of the caspase 9a splice variant in PC3 prostate cancer cells. Int J Oncol. 2013 Jul;43(1):194-200.
  43. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001 Jun 1;47(4):293-303.
  44. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. Aaps j. 2013 Jan;15(1):195-218.
  45. Rao KV, Samikkannu T, Dakshayani KB, et al. Chemopreventive potential of an ethyl acetate fraction from Curcuma longa is associated with upregulation of p57(kip2) and Rad9 in the PC-3M prostate cancer cell line. Asian Pac J Cancer Prev. 2012;13(3): 1031-8.
  46. Cheng TS, Chen WC, Lin YY, et al. Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res (Phila). 2013 May;6(5):495-505.
  47. Killian PH, Kronski E, Michalik KM, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis. 2012 Dec;33(12):2507-19.
  48. Sundram V, Chauhan SC, Ebeling M, Jaggi M. Curcumin attenuates beta-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One. 2012;7(4):e35368.
  49. Herman JG, Stadelman HL, Roselli CE. Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. Int J Oncol. 2009 May;34(5):1319-27.
  50. Yang L, Zhang LY, Chen WW, et al. Inhibition of the expression of prostate specific antigen by curcumin. Yao Xue Xue Bao. 2005 Sep;40(9):800-3.
  51. Chung LC, Tsui KH, Feng TH, Lee SL, Chang PL, Juang HH. Curcumin provides potential protection against the activation of hypoxia and prolyl 4-hydroxylase inhibitors on prostate-specific antigen expression in human prostate carcinoma cells. Mol Nutr Food Res. 2011 Nov;55(11):1666-76.
  52. Tsui KH, Feng TH, Lin CM, Chang PL, Juang HH. Curcumin blocks the activation of androgen and interlukin-6 on prostate-specific antigen expression in human prostatic carcinoma cells. J Androl. 2008 Nov-Dec;29(6):661-8.
  53. Choi HY, Lim JE, Hong JH. Curcumin interrupts the interaction between the androgen receptor and Wnt/beta-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 2010 Dec;13(4):343-9.
  54. Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res. 2013 Jul 12.
  55. Teiten MH, Gaascht F, Cronauer M, Henry E, Dicato M, Diederich M. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol. 2011 Mar;38(3):603-11.
  56. Guo H, Xu YM, Ye ZQ, Yu JH, Hu XY. Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. Pharmazie. 2013 Jun;68(6):431-4.
  57. Shankar S, Ganapathy S, Chen Q, Srivastava RK. Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer. 2008;7:16.
  58. Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene. 2004 Feb 26;23(8):1599-607.
  59. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62(7):919-30.
  60. Hung CM, Su YH, Lin HY, et al. Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. J Agric Food Chem. 2012 Aug 16.
  61. Shah S, Prasad S, Knudsen KE. Targeting pioneering factor and hormone receptor cooperative pathways to suppress tumor progression. Cancer Res. 2012 Mar 1;72(5):1248-59.
  62. Teiten MH, Gaigneaux A, Chateauvieux S, et al. Identification of differentially expressed proteins in curcumin-treated prostate cancer cell lines. Omics. 2012 Jun;16(6):289-300.
  63. Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res. 2011 Jul;55(7):999-1009.
  64. Rogan EG. The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006 Mar-Apr;20(2):221-8.
  65. Joseph MA, Moysich KB, Freudenheim JL, et al. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 2004;50(2):206-13.
  66. Abdull Razis AF, Noor NM. Cruciferous vegetables: dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev. 2013;14(3):1565-70.
  67. Dashwood RH, Ho E. Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363-9.
  68. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007 Feb;232(2):227-34.
  69. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. Faseb j. 2006 Mar;20(3):506-8.
  70. Gryder BE, Rood MK, Johnson KA, et al. Histone deacetylase inhibitors equipped with estrogen receptor modulation activity. J Med Chem. 2013 Jul 3.
  71. Stettner M, Kramer G, Strauss A, et al. Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer. Eur J Cancer Prev. 2012 Jan;21(1):55-64.
  72. Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst. 2007 Aug 1;99(15):1200-9.
  73. Canene-Adams K, Lindshield BL, Wang S, Jeffery EH, Clinton SK, Erdman JW, Jr. Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. Cancer Res. 2007 Jan 15;67(2):836-43.
  74. Zhang J, Hsu BAJ, Kinseth BAM, Bjeldanes LF, Firestone GL. Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells. Cancer. 2003 Dec 1;98(11):2511-20.
  75. Chiao JW, Chung FL, Kancherla R, Ahmed T, Mittelman A, Conaway CC. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol. 2002 Mar;20(3):631-6.
  76. Han HY, Shan S, Zhang X, Wang NL, Lu XP, Yao XS. Down-regulation of prostate specific antigen in LNCaP cells by flavonoids from the pollen of Brassica napus L. Phytomedicine. 2007 May;14(5):338-43.
  77. Traka MH, Spinks CA, Doleman JF, et al. The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer. Mol Cancer. 2010;9:189.
  78. Melchini A, Traka MH, Catania S, et al. Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells. Nutr Cancer. 2013;65(1):132-8.
  79. Hahm ER, Singh SV. Sulforaphane inhibits constitutive and interleukin-6-induced activation of signal transducer and activator of transcription 3 in prostate cancer cells. Cancer Prev Res (Phila). 2010 Apr;3(4):484-94.
  80. Choi S, Singh SV. Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent. Cancer Res. 2005 Mar 1;65(5):2035-43.
  81. Ho E, Clarke JD, Dashwood RH. Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention. J Nutr. 2009 Dec;139(12):2393-6.
  82. Traka M, Gasper AV, Melchini A, et al. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS One. 2008;3(7):e2568.
  83. Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database Syst Rev. 2013;1:Cd004720.
  84. Van Neste L, Herman JG, Otto G, Bigley JW, Epstein JI, Van Criekinge W. The epigenetic promise for prostate cancer diagnosis. Prostate. 2012 Aug 1;72(11):1248-61.
  85. Benchikh El Fegoun A, Villers A, Moreau JL, Richaud P, Rebillard X, Beuzeboc P. PSA and follow-up after treatment of prostate cancer. Prog Urol. 2008 Mar;18(3):137-44.