Life Extension Magazine June 2005
As We See It
Does PSA Promote Prostate Cancer?
By William Faloon
Aging men should consider having their blood tested for DHT. If DHT levels are elevated, Avodart® drug therapy appears to be safe and effective not only for improving urinary flow symptoms, but more importantly for potentially reducing prostate cancer risk. Avodart® appears to accomplish these effects by reducing the growth-promoting effects of DHT on prostatic tissue, while decreasing the cancer-inducing properties of PSA by reducing PSA synthesis in the prostate gland.
Avodart® does have several downsides. At more than $3 per capsule, it is expensive. Moreover, a small percentage of men who use it have sexual dysfunction problems such as decreased libido (4%), impotence (7%), and a decreased volume of ejaculate (2%). The frequency of these side effects reportedly decline after six months of continued use of Avodart®.
Blocking PSA’s Detrimental Effects Naturally
There may be another way to protect the prostate gland against its own PSA. Since consuming green tea has been reported to lower the risk of prostate cancer, scientists investigated the effects of the green tea flavonoid epigallocatechin gallate (EGCG) on the expression and activity of PSA by prostate cancer cells. In addition to restraining PSA expression, EGCG inhibited numerous cancer-promoting properties of PSA in a dose-dependent manner. EGCG inhibited tumor-promoting activities such as degradation of type IV collagen. EGCG’s beneficial effects were at blood levels close to those measured in serum following ingestion of green tea.38 The study authors proposed that green tea extract may be a natural inhibitor of prostate carcinoma aggressiveness.
Effects of Soy on PSA Levels
Another potential way to lower PSA levels is to increase soy consumption. It has long been known that human populations that consume soy products have a lower risk of prostate cancer.9,39
Scientists have evaluated soy’s effects on PSA and other prostate cancer-related blood markers in men who had already developed prostate cancer.40 A group of 29 men scheduled to undergo surgical removal of the prostate were put on a 50-gram soy bread supplement or a 50-gram wheat supplement. The soy group saw a 12.7% reduction in PSA levels, whereas the wheat group experienced a 40% increase in cancer-promoting PSA. The free/total PSA ratio increased by 27.4% in the soy-supplemented group, compared to a decrease of 15.6% in the wheat group. (A higher free/total PSA ratio is a favorable indicator.) The investigators concluded that men who consume diets high in soy might have a reduced risk of prostate cancer development and progression.
Curcumin Induces Cancer Cell Suicide
Cancer cells do not follow normal, healthy cell suicide programs. Old cells need to die and be discarded, but cancer cells proliferate and grow.
Numerous studies over the past two years have identified specific mechanisms by which curcumin inhibits the growth of prostate cancer cells and then activates genes that tell cancer cells to self-destruct (also referred to as apoptosis).41,42 One study showed that curcumin reprograms prostate cancer cells so as to make them less likely to metastasize to the bone, while another study demonstrated that curcumin has radiation-sensitizing effects, making cancer cells more vulnerable to destruction by conventional radiation therapy.43,44 The research on curcumin is so promising that pharmaceutical companies are currently developing curcumin analogs that can be patented as anti-cancer therapies.45,46
Critical Importance of Annual PSA Testing
In 2004, the New England Journal of Medicine published an article indicating that the rate of increase in PSA is a more important predictor of mortality than the PSA reading itself. Men who showed a 2.0 ng/ml or greater increase in PSA from the previous year’s level were 10 times more likely to die within seven years.47 The researchers recommended that men over the age of 35 should have a baseline PSA reading and then retest each year to measure the rate of increase (PSA velocity). A sharp rise in PSA mandates the need for more comprehensive evaluation and treatment. Without previous PSA readings, it is impossible for your doctor to calculate PSA velocity. Optimal measurement of PSA velocity requires at least three PSA readings, with each obtained at least six months apart and tested at the same laboratory using the same PSA laboratory procedure.
In summary, accumulating data suggest that PSA is no longer merely a laboratory test of prostate gland activity. Instead, PSA is recognized as a functional protein: an enzyme that may facilitate prostate cancer cell proliferation, invasion, and metastasis. Taking steps to suppress PSA may reduce prostate cancer risk and progression. Meaningful reductions in PSA, as demonstrated in many of the studies cited in this article, appear achievable by using natural supplements like lycopene, soy, green tea, and boron, as well as through prescription drugs such as Avodart® or Proscar®, which normally reduce serum PSA levels by 40-50%.48-50
Low-Cost Blood Testing
A number of blood tests can identify correctable risk factors before clinically advanced disease becomes established. Most people test their blood to ascertain levels of cardiovascular disease markers such as homocysteine, C-reactive protein, LDL (low-density lipoprotein), and HDL (high-density lipoprotein).
While the PSA test has become well known, some men have been reluctant to have it done for fear that it will reveal a problem that cannot be easily corrected. Over the past few years, however, a significant number of publications have revealed safe methods of lowering PSA and potentially reducing prostate cancer risk.
Until June 1, 2005, Life Extension members can obtain comprehensive blood test panels at extra-low discounted prices. The popular Male Panel includes the PSA test, along with homocysteine, DHEA sulfate, C-reactive protein, and numerous other tests. It does not, however, include the dihydrotestosterone (DHT) test that would be of significant importance if PSA levels were in any way elevated.
High DHT levels stimulate the androgen receptor to induce greater PSA production.51 DHT also interacts with extracellular tissues to increase prostate cancer cell mobility.52 These and other findings may well be the basis for the reduction in prostate cancer development seen in men treated with inhibitors of DHT. The normal retail price for the DHT test is $60, but during the annual blood test sale, members pay only $23 for this test.
If you have delayed ordering your annual blood test panel, please do not wait any longer, as the Blood Test Super Sale ends on June 1, 2005. Now more than ever before, determining your PSA (and DHT) levels may dramatically reduce your odds of becoming a prostate cancer victim.
For longer life,
1. Gallardo-Williams MT, Maronpot RR, Wine RN, Brunssen SH, Chapin RE. Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid. Prostate. 2003 Jan 1;54(1):44-9. PMID 12481254
2. Cohen P, Graves HC, Peehl DM, et al. Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma. J Clin Endocrinol Metab. 1992 Oct;75(4):1046-53. PMID 1383255
3. Cohen P, Peehl DM, Graves HC, Rosenfeld RG. Biological effects of prostate specific antigen as an insulin-like growth factor binding protein-3 protease. J Endocrinol. 1994 Sep;142(3):407-15. PMID 7525824
4. Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst. 1995 Dec 6;87(23):1767-76. PMID 7473833
5. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998 Mar 18;90(6):440-6. PMID 9521168
6. Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23. PMID 11121464
7. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood.). 2002 Nov;227(10):852-9. PMID 12424325
8. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002 Mar 6;94(5):391-8. PMID 11880478
9. Lee MM, Gomez SL, Chang JS, et al. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):665-8. PMID 12869409
10. Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer. 2004 Jan 1;108(1):130-5. PMID 14618627
11. Leitzmann MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004 Jul;80(1):204-16. PMID 15213050
12. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004 Apr;11(4):887-92. PMID 15010890
13. Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int. 2003 Sep;92(4):375-8. PMID 12930422
14. Ansari MS, Gupta NP. Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. Urol Oncol. 2004 Sep;22(5):415-20. PMID 15464923
15. Thiel R, Effert P. Primary adenocarcinoma of the seminal vesicles. J Urol. 2002 Nov;168(5):1891-6. PMID 12394673
16. Holund B. Latent prostatic cancer in a consecutive autopsy series. Scand J Urol Nephrol. 1980;14(1):29-35. PMID 6154966
17. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol. 1993 Aug;150(2 Pt 1):379-85. PMID 8326560
18. Partin AW, Pound CR, Clemens JQ, Epstein JI, Walsh PC. Serum PSA after anatomic radical prostatectomy. The Johns Hopkins experience after 10 years. Urol Clin North Am. 1993 Nov;20(4):713-25. PMID 7505980
19. Pound CR, Partin AW, Epstein JI, Walsh PC. Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol Clin North Am. 1997 May;24(2):395-406. PMID 9126237
20. Hanlon AL, Hanks GE. Failure patterns and hazard rates for failure suggest the cure of prostate cancer by external beam radiation. Urology. 2000 May;55(5):725-9. PMID 10792090
21. Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am. 2001 Aug;28(3):555-65. PMID 11590814
22. Hanks GE, Hanlon AL, Epstein B, Horwitz EM. Dose response in prostate cancer with 8-12 years’ follow-up. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):427-35. PMID 12243818
23. Kupelian PA, Potters L, Khuntia D, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):25-33. PMID 14697417
24. Jones EC, McNeal J, Bruchovsky N, de Jong G. DNA content in prostatic adenocarcinoma. A flow cytometry study of the predictive value of aneuploidy for tumor volume, percentage Gleason grade 4 and 5, and lymph node metastases. Cancer. 1990 Aug 15;66(4):752-7. PMID 2386930
25. Deitch AD, Miller GJ, deVere White RW. Significance of abnormal diploid DNA histograms in localized prostate cancer and adjacent benign prostatic tissue. Cancer. 1993 Sep 1;72(5):1692-700. PMID 7688657
26. Perlman EJ, Epstein JI, Long PP, Pizov G, Griffin CA. Cytogenetic and ploidy analysis of prostatic adenocarcinoma. Mod Pathol. 1993 May;6(3):348-52. PMID 8346183
27. Shankey TV, Jin JK, Dougherty S, et al. DNA ploidy and proliferation heterogeneity in human prostate cancers. Cytometry. 1995 Sep 1;21(1):30-9. PMID 8529468
28. Bowen P, Chen L, Stacewicz-Sapuntzakis M, et al. Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis. Exp Biol Med (Maywood.). 2002 Nov;227(10):886-93. PMID 12424330
29. Gallardo-Williams MT, Chapin RE, King PE, et al. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004 Jan;32(1):73-8. PMID 14713551
30. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004 Dec 8;216(1):21-9. PMID 15500945
31. Geller J, Sionit L. Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride. J Cell Biochem Suppl. 1992;16H:109-12. PMID 1283893
32. Deslypere JP, Young M, Wilson JD, McPhaul MJ. Testosterone and 5 alpha-dihydrotestosterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene. Mol Cell Endocrinol. 1992 Oct;88(1-3):15-22. PMID 1334007
33. Wright AS, Thomas LN, Douglas RC, Lazier CB, Rittmaster RS. Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat. J Clin Invest. 1996 Dec 1;98(11):2558-63. PMID 8958218
34. Andriole GL, Humphrey P, Ray P, et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004 Sep;172(3):915-9. PMID 15310997
35. Lazier CB, Thomas LN, Douglas RC, Vessey JP, Rittmaster RS. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004 Feb 1;58(2):130-44. PMID 14716738
36. Andriole GL, Roehrborn C, Schulman C, et al. Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia. Urology. 2004 Sep;64(3):537-41. PMID 15351586
37. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24. PMID 12824459
38. 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. PMID 15386386
39. Sonoda T, Nagata Y, Mori M, et al. A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet. Cancer Sci. 2004 Mar;95(3):238-42. PMID 15016323
40. Dalais FS, Meliala A, Wattanapenpaiboon N, et al. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology. 2004 Sep;64(3):510-5. PMID 15351581
41. Deeb D, Xu YX, Jiang H, et al. Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther. 2003 Jan;2(1):95-103. PMID 12533677
42. Deeb D, Jiang H, Gao X, et al. Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through suppression of IkappaBalpha phosphorylation. Mol Cancer Ther. 2004 Jul;3(7):803-12. PMID 15252141
43. 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. PMID 14985701
44. Dorai T, Dutcher JP, Dempster DW, Wiernik PH. Therapeutic potential of curcumin in prostate cancer—V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate. 2004 Jun 15;60(1):1-17. PMID 15129424
45. Adams BK, Ferstl EM, Davis MC, et al. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg Med Chem. 2004 Jul 15;12(14):3871-83. PMID 15210154
46. Adams BK, Cai J, Armstrong J, et al. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs. 2005 Mar;16(3):263-75. PMID 15711178
47. D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004 Jul 8;351(2):125-35. PMID 15247353
48. Cote RJ, Skinner EC, Salem CE, et al. The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels. Br J Cancer. 1998 Aug;78(3):413-8. PMID 9703292
49. Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol. 2003 Jul;44(1):82-8. PMID 12814679
50. Lowe FC, McConnell JD, Hudson PB, et al. Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Urology. 2003 Apr;61(4):791-6. PMID 12670567
51. Lee C, Sutkowski DM, Sensibar JA, et al. Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology. 1995 Feb;136(2):796-803. PMID 7530653
52. Murphy BC, Pienta KJ, Coffey DS. Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells. Prostate. 1992;20(1):29-41. PMID 1371008