Add as bookmark

Complementary Therapies for Hormone Refractory Prostrate Cancer

by Prof Ben L. Pfeifer MD PhD(more info)

listed in cancer, originally published in issue 120 - February 2006

There is an ever-increasing demand for complementary therapies by patients with prostate cancer. Often, patients' expectations of such treatments are too high. In particular, complementary treatment cannot replace the potentially curative methods such as radical prostatectomy and radiation therapy. During the early stages of the disease, when cancer growth is still confined to the prostate, complementary treatments are primarily intended to enhance recognized standard therapy practices. During the hormone refractory stage of the disease, however, complementary treatment has gained significance due to its low toxicity.

Complementary Therapies for Hormone Refractory Prostrate Cancer

Prostate Cancer – Where do we Stand Today?

Prostate cancer is today the most frequent malignant tumour in men – more frequent than lung cancer. In the UK, 32,000 new cases are registered each year. In about 50% of these cases it can be expected that the disease progresses to an incurable stage and that in ten percent to 20% of the cases metastases can already be verified at the time of primary diagnosis.[1] More than 10,000 men die each year from prostate cancer in the UK, the disease representing around 13% of the approximately 77,000 male deaths from cancer in this country. The prevalence of the disease is, however, much higher, since only a small number of prostate cancer cases is ever diagnosed due to slow growth and late appearance of the tumour. The increase in incidence can mainly be considered the result of improved screening procedure by means of prostate specific antigen (PSA). Since mainly older men are affected by prostate cancer, and the age structure of most West European industrial societies continues to move towards longer life expectancy, the number of new cases of the most frequent type of cancer in men will also continue to increase. This trend is alarming; as we presently cannot offer any treatment for this disease which we know for sure will lead to cure, prolong life expectancy, or at least do the patient more good than evil. Demands will be made by increasingly better informed and critical patients on urologists, radiologists and oncologists to provide competent and objective information on the advantages and disadvantages of the therapeutic options available. This also includes complementary therapies, as more and more patients today are looking for less traumatic and less toxic treatment.[2-6]

Present day potentially curative therapies, such as radical prostatectomy and radiation treatment, only make sense as long as the cancer is confined to the prostate and metastases have not developed. Unfortunately, these treatment methods lead in a high percentage of cases to unacceptable and permanent side-effects, e.g. erectile impotency in 60%-100%, rectal disorders in 15%-40% and urinary incontinence in 10%-30% of patients.[7-11] Furthermore, with regard to 'cure', the results of treatment by these invasive methods are still unsatisfactory; recurrence rates of between 20%- 50% are reported.[12-17] The curative effect of local treatment methods, such as radical operation and radiation therapy, are largely dependent on correct patient selection. Current customary diagnostic procedures, however, often underestimate the extent of the disease, so that patients receiving surgery or radiation treatment are in reality no longer candidates for these methods of treatment, because their prostate cancer has spread from the organ and has already formed micrometastases.

There is presently still no cure for metastatic prostate cancer,[18][,][19] and the testosterone ablating therapies such as orchidectomy or the administration of LHRH agonists and anti-androgens frequently only achieve short-term tumour control (months to a few years). Long-term results are unsatisfactory and most prostate cancer patients become hormone refractory. At this stage there is often fast progression of the disease and metastases develop. Various lines of initial treatment, such as newer combinations of chemotherapy, use of radioisotopes (e.g. samarium-153), blocking of growth factors by monoclonal antibodies, immune therapies (e.g. dendritic cell vaccines), angiogenesis blocking strategies, re-differentiation of cancer cells by means of retinoids and vitamin D analogues and finally gene therapy, are presently undergoing clinical trials for this particular situation, but up to now none of these measures has brought patients significant advantages.

Complementary Treatment Methods

Due especially to the unpleasant and often permanent side-effects and the high rate of treatment failure, many patients with prostate cancer seek alternative or complementary treatment methods. Their expectations are often unrealistic, as many complementary treatment methods are advocated without proof of efficacy regarding inhibition of cancer growth or prolongation of life. During the early stages of the disease (cancerous growth limited to the prostate) complementary therapies are primarily intended to enhance recognized standard practices. For patients with metastases and the development of a hormone refractory stage, the situation is somewhat different. An increasing number of patients are requesting solely complementary treatment to avoid the frequently toxic effects of chemotherapy. The following treatment consisting of a combination of phytotherapy, immune therapy and antioxidative/orthomolecular therapy has proven for us to be exceptionally effective:

Phytotherapy with Prostasol and Curcumin complex

Prostasol is available in the UK, on the European market and in the US as a food supplement. It consists of various sitosterols (camptosterol, stimgasterol, brassicasterol), Quercetin (phytooestrogen, flavonoid), Pygeum africanum (pygeum), Serenoa repens (saw palmetto), Panax pseudoginseng (ginseng), Zingiber officinale (ginger), Urtica diotica (stinging nettle), Scutellaria (scull cap) and Ganoderma lucidum (filamentous fungi). Laboratory tests on Prostasol in two independent laboratories in Switzerland detected neither synthetic ingredients, such as oestrogens, anti-inflammatory drugs, glucocorticoids or narcotics, nor any heavy metal pollutants or pesticides.[20] Following oral intake of 900 to 2800 mg of Prostasol there is a > 50% drop within a few months in the PSA reading in approximately 70% of hormone refractory prostate cancer patients (see Fig. 1 and 3). This sort of decrease is often associated with a decline in metastatic pain and a general improvement in quality of life.[21] In about one third of the patients there is a decrease in tumour mass in the primary tumour and/or the metastases (see Figs. 4a,b-5a,b). Blood count, coagulation parameters, serum electrolytes, serum enzymes (SGPT, SGOT, alkaline phosphatase, gamma GT), as well as bilirubin, creatine and uric acid levels remain unchanged during the intake of Prostasol. There are few side-effects on the whole and these consist of increased sensitivity of the breast nipples during the first two months of intake in about 40% of the patients, bloating in about ten percent and short-term diarrhoea in about five percent of the cases. Superficial leg vein thrombosis is reported in less than one percent of patients,[22] although a causal connection here is unclear, since the disease itself increases the risk of thrombosis.

Experimental research has proven that most constituents of Prostasol can block cancer growth and are capable of inducing apoptosis in prostate cancer cells. Phytosterols such as camptosterol and beta-sitosterol, which occur in large quantities in vegetables and fruit, do in fact have strong antioxidative effects and increase the apoptosis rate in human prostate cancer cells (LNCaP) fourfold.[23] In animal experiments, these phytosterols prevented both growth and metastases of transplanted human prostate cancer cells.[24] An immune stimulating effect in humans by phytosterols has been verified with an increase in T and NK cells in peripheral blood following intake during four weeks.[25] Recently, Chan et al[26] showed that extracts of scutellaria contain the flavonoid baicalin which at lowest concentrations already causes 50% apoptosis in DU145 prostate cancer cells. Stinging nettle extracts are known to suppress the growth of prostate cancer cells. Lichius et al[27] were able to determine that the polysaccharide fraction of a 20% methanol extraction of stinging nettle root blocked the growth of prostate carcinoma cells from lymph gland metastases by 50%. Other components of Prostasol are known to possess anti-tumour properties. For example, ganoderma is described as developing its anti-tumour effect by releasing cytokines such as TNF-alpha and INF-gamma.[28] Knowles, et al[29] have reported that already 100 micromoles of quercetin lead to a complete growth inhibition in hormone resistant prostate cancer cells (PC-3 cell culture). Surh[30] made known that the phenols 6-ginerol and 6-paradol that are present in ginger have a distinct anti-tumour effect. Liu, et al[31] have proved that saponin and ginsenosid (Rg-3), extracted from ginseng, bring about a significant decline in prostate cancer cells associated with a reduction in PSA and androgen-receptor expression. Furthermore, ginseng extracts also caused classical apoptosis by inhibition of bcl-2 gene activity, and also significantly reduced the metastatic potential of prostate cancer cells. Iguchi and co-workers also described a similarly strong apoptic effect of Serenoa repens extract, which at least in part is based on the cytotoxic properties of myristoleic acid.[32]

Curcumin complex consists of a standardized quantity of curcumin, bioperin and resveratrol. Curcumin is an extract of the turmeric root and known as a tyrosin kinase inhibitor with documented efficacy against cancer cells in general[33,34] and against prostate cancer cells in-vitro and in-vivo in particular.[35-39] By suppressing the cell 'survival' factors NF-kappaB and the so-called Akt factor (signal protein kinase) and by influencing growth factors, curcumin can apparently intervene in the cell cycle of prostate cancer cells and thus lead to inhibition of cell division and apoptosis. Bioperin, a black pepper extract, is a known inhibitor of glucoronidase in the gastrointestinal tract and in the liver. This substance improves the absorption of curcumin and its bioavailability in humans by over 2,000% without producing side-effects.[40] Resveratrol is found in grapes and is a phytoalexin with pronounced antioxidative and cancer inhibiting properties. Even at micromolar concentrations, it inhibits growth and induces apoptosis in hormone sensitive as well as hormone refractory prostate cancer cells.[41-43] In particular, a combination of resveratrol and beta-sitosterol (main component of Prostasol) triggers distinct inhibition of cancer growth, possibly by inducing apoptosis, directly blocking cell division and affecting prostaglandin synthesis.[44]

Antioxidative/Orthomolecular Therapy with IMUPROS

IMUPROS™ is available in Europe and the UK as a food supplement. It contains an antioxidative combination of vitamins and trace elements, as well as a proprietary mixture of genistein, lycopene and epigallocatechin gallate. The manufacturer claims that the single active ingredients are from natural sources only. A special manufacturing process (time-release coatings) ensures that the single active ingredients do not interact within the capsule. The single ingredients are released at varying times into the gastrointestinal tract, allowing undisturbed reabsorbtion into the blood and improving bioavailability. Selenium and vitamin E are two important components of this combination of agents. Selenium activates the phase 2 enzyme glutathione peroxidase in the cell and thus boosts the elimination of free oxygen radicals.[45] The recently published results of the Nutritional Prevention of Cancer (NPC) Trial in the US have shown a distinct reduction in the frequency of prostate cancer by selenium substitution with 0.2 mg per day.[46] Similar effects were shown in earlier studies where selenium substitution versus placebo reduced the risk of prostate cancer by approximately 60%.[47-49] The preventive effect of vitamin E was investigated in the Alpha tocopherol, Beta-carotene Cancer Prevention Study. Here, among almost 30,000 men at the age of 50-69 years, a daily intake of 50 mg of alpha tocopherol reduced prostate cancer incidence by 32% and prostate-related mortality by 41%.[50] These results, however, were from patients with low initial plasma selenium values who were smokers. Whether men with normal selenium levels who are non-smokers would benefit from selenium and vitamin E substitution remains unclear.[51] The worldwide largest prostate cancer prevention study 'SELECT',[52] which started in August 2001 in the US, should now resolve this doubt and reveal whether selenium and vitamin E guard against prostate cancer. A total of 32,400 men are to take part in this double-blind, randomized and placebo controlled study over a period of 12 years. Epigallocatechin gallate (EGCG), a polyphenol in green tea (Camellia sinensis), has stronger antioxidative properties than vitamin E and C. Experimental investigations have shown that EGCG can modulate the androgen effect,[53] intervene at various points in the prostate cancer cell cycle,[54,55] and induce apoptosis both in androgen-sensitive and androgen-refractory prostate cancer cell cultures.[56] Furthermore, ECGC retards the angiogenesis by decreasing interleucin-8 and VE-cadherin production and acts anti-metastatically in animal models with transplanted prostate cancer.[57,58] Lycopene, a carotenoid with particularly strong antioxidative effects has become very popular in recent years in the prevention of prostate cancer. Dosage-related suppression of growth by lycopene in prostate cancer cell cultures has been verified.[59] A diet rich in lycopene reduces DNA damage caused by oxidative stress and decreases PSA values by approximately 17% in patients with prostate cancer.[60] IMUPROS™ has no side-effects and is well tolerated.

As an added advantage it allows a drastic reduction in the daily amount of tablets or capsules otherwise required if the above mentioned active ingredients are designed as preventive or supportive therapy for prostate cancer. Whilst previously patients had to take approximately 20-30 tablets or capsules of the active ingredients daily, three to six tablets of IMUPROS™ per day already provide a comparable dosage of active ingredient for complementary therapy.

Immunotherapy with Biobran and Mistletoe Extract

The stimulation of specific immune system functions is a sensible treatment strategy with prostate cancer. Experimental studies in active and passive immunotherapy, especially the use of so-called dendritic cell vaccines, have not only confirmed the basic theoretical approach,[61-63] but have also led to clinical results.[64-65] The aim of immunological therapies is to improve the immune response of cytotoxic T cells to prostate cancer. Arabinoxylan, the immunostimulant in Biobran, causes a significant rise in the number and activity of T and B cells, as well as natural killer cells (NK cells). This has been proved in both animal experiments[66,67] and prostate cancer patients (see Fig. 2). Furthermore, Biobran increases macrophage activity, leading to a consecutive increase in TNF alpha and IL 6.[68] Therefore, through the increased activity by arabinoxylan in both the humeral and cellular immune systems, an improved immune response is achieved.

We use Biobran on patients with hormone refractory prostate cancer in a dosage of 15-30 mg/kg/day, not only in combination with the above described phytotherapy, but also together with chemotherapy or radiation treatment in the hope of improving immune defence mechanisms and decreasing therapy-related side-effects. At present, however, no placebo-controlled studies exist on the efficacy of Biobran in prostate carcinoma.

The administration of mistletoe extract is today the most frequent complementary measure in oncological practice. At present, both standardized mistletoe extract and lectin preparations are in use. Mistletoe therapy causes unspecific stimulation of the immune system by activation of macrophages, neutrophile granulocytes and NK cells, as well as the release of TNF-alpha, GM-CSF and various interleukins. In addition, mistletoe lectins have a certain cytotoxic effect by inhibiting ribosomal protein synthesis (similar to ricin and abrin). Finally, mistletoe lectins increase the release of beta-endorphins, which possibly could account for the improvement in wellbeing (increased appetite, better sleep, less pain, improved performance) experienced under mistletoe therapy.[69-70] Although mistletoe alone cannot decrease the PSA value with either androgen sensitive or androgen refractory prostate cancer, it can be presumed that both the immune defense functions and the quality of life for patients with prostate cancer can be enhanced as has been proven for colorectal carcinomas[71] and gliomas.[72] More recent studies confer new values on lectin standardized mistletoe therapy in the area of evidence based medicine. A retrolective cohort study on 689 patients with breast cancer was able to establish a significant reduction in tumour and therapy-related disorders (e.g. nausea and vomiting, weakness, loss of appetite), as well as a trend towards prolongation of the recurrence-free survival time.[73]

Dietary Measures

It is estimated that about 35%- 40% of all cancers are partly caused by poor or insufficient nutrition.[74] Nutritional consultation and education, therefore, seems a sensible measure within the framework of primary and secondary prevention of cancer in general, as well as in the specific example of complementary therapy for prostate cancer. Too high a calorie intake per day, and the obesity often associated with it, will not only increase the risk of prostate cancer, but also increase the death rate of this disease.[75-77] Restricting calorie intake in animal experiments can prevent the development of cancer and arrest its growth.[78] Asian men have a much lower incidence of prostate cancer than men living in western cultures.[79] Vegetarians also seem to suffer less from prostate cancer.[80] Both Asians and vegetarians consume less fat but a greater share of plant foods, which as a preventive measure and during treatment for prostate cancer can certainly be regarded as a desirable dietary directive. The role of fat intake in prostate cancer genesis remains controversial.[81,82] In particular, saturated fats in meat, milk and cheese are however linked with an increased risk of prostate cancer.[83,84] An increase in the testosterone level of the blood following fat intake,[85] and the direct influence on the activity of nuclear receptors in the prostate cell do in all probability play a role in this process. Arachidonic acid, linolenic acid and alpha-linolenic acid are those polysaturated fats occurring in margarine and salad oils which are considered possible risk factors for the development of prostate cancer. In particular arachidonic acid, an omega-6 fatty acid, presents a potential risk due to its possible conversion into 5-HETE and 12-HETE, as these biologically active fats stimulate both the growth and survival of prostate cancer cells and also increase the invasive capability of these cells and angiogenesis in the tumour region.[86] A change of diet from meat, milk and cheese to a mainly vegetarian diet can reduce the blood level of arachidonic acid by 80%-90% within a period of two to three months. Restricting the consumption of dairy products and the ensuing decrease in the daily intake of calcium also helps reduce the risk of prostate cancer.[87] Apart from an appropriate decrease in excessive calorie intake and a reduction in the proportion of animal fats in the diet, the abundant intake of fresh fruit and vegetables plays a role in the prevention and treatment of prostate cancer. Although on the whole, evidence of the protective effect of fruit and vegetables is weak, a recent multicentric study on over 1,600 patients showed that in particular, peas, beans, lentils and soya beans, together with yellow and orange-coloured vegetables, will provide a protective effect with regard to prostate cancer.[88] Is it possible to derive and recommend a workable 'prostate diet' from what has just been discussed? We think so, and recommend to our patients a reduction in their total calorie intake and in animal fats in their diet. Furthermore, we also recommend restricting the intake of dairy products and at the same time increasing their intake of fresh fruit and vegetables.

Critical Evaluation

The complementary therapeutic measures for patients with hormone refractory prostate cancer presented here are the subject of controversial discussion in urological and oncological circles, primarily because definite evidence of the clinical efficacy of many of the preparations and treatment methods mentioned here is not yet available. Phytotherapy with Prostasol and Curcumin complex, the antioxidative and dietary measures and the immune support programme described cannot replace recognized standard therapies for prostate cancer, in particular for patients in the initial stages of the disease. However, since at present, no effective standard therapy for the hormone refractory stage of prostate cancer exists, and previous clinical experience with these complementary measures has led to a biochemical and clinical response in two-thirds of the patients, we consider the implementation of the complementary measures described here for this patient group to be fully justifiable. The systematic investigation in controlled clinical studies of the effect of these therapeutic measures with regard to quality of life and prolongation of life is a highly desirable objective.


2. Eng J, Ramsum D, Verhoef M, Guns E, Davison J and Gallagher R. A population-based survey of complementary and alternative medicine use in men recently diagnosed with prostate cancer. Integr Cancer Ther. 2: 212-216. 2003.
3. Uzzo RG, Brown JG, Horwitz EM, Hanlon A, Mazzoni S, Konski A, Greenberg RE, Pollack A, Kolenko V and Watkins-Bruner D. Prevalence and patterns of self-initiated nutritional supplementation in men at high risk of prostate cancer. BJU Int. 93: 955-60. 2004.
4. Huber R, Koch D, Beiser I, Zschocke I and Luedtke R. Experience and attitudes towards CAM – a survey of internal and psychosomatic patients in a German university hospital. Altern Ther Health Med. 10: 32-36. 2004.
5. Boon H, Westlake K, Stewart M, Gray R, Fleshner N, Gavin A, Brown JB and Goel V. Use of complementary/alternative medicine by men diagnosed with prostate cancer: prevalence and characteristics. Urology. 62: 849-853. 2003.
6. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR and Delbanco TL. Unconventional medicine in the United States: prevalence, costs, and patterns of use. N Engl J Med. 328: 246-252. 1993.
7. Lilleby W, Fossa SD, Waehre HR and Olsen DR. Long-term morbidity and quality of life in patients with localized prostate cancer undergoing definitive radiotherapy or radical prostatectomy. Int J Radiat Oncol Biol Phys. 43: 735-743. 1999.
8. Potosky AL, Davis WW, Hoffman RM, Stanford JL, Stephenson RA, Penson DF and Harlan LC. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst. 96: 1358-1367. 2004.
9. van Andel G, Visser AP, Zwinderman AH, Hulshof MC, Horenblas S and Kurth KH. A prospective longitudinal study comparing the impact of external radiation therapy with radical prostatectomy on health related quality of life (HRQOL) in prostate cancer patients. Prostate. 58: 354-365. 2004.
10. Lepor H, Kaci L. The impact of open radical retropubic prostatectomy on continence and lower urinary tract symptoms: a prospective assessment using validated self-administered outcome instruments. J Urol. 171: 1216-1219. 2004.
11. Salomon L, Saint F, Anastasiadis AG, Sebe P, Chopin D and Abbou CC. Combined reporting of cancer control and functional results of radical prostatectomy. Eur Urol. 44: 656-60. 2003.
12. Roehl KA, Han M, Ramos CG, Antenor JA and Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 172: 910-914. 2004.
13. Winkler MH, Khan FA, Shabir M, Okeke A, Sugiono M, McInerney P, Boustead GB, Persad R, Kaisary AV and Gillatt DA. Contemporary update of cancer control after radical prostatectomy in the UK. Br J Cancer. 91: 1853-1857. 2004.
14. Potters L, Klein EA, Kattan MW, Reddy CA, Ciezki JP, Reuther AM and Kupelian PA. Monotherapy for stage T1-T2 prostate cancer: radical prostatectomy, external beam radiotherapy, or permanent seed implantation. Radiotherapy and Oncology. 71: 29-33. 2004.
15. Partin AW, Pound CR, Clemens JQ, Epstein JI and Walsh PC. Serum PSA after anatomic radical prostatectomy. The John Hopkins experience after ten years. Urol Clin North Am. 20: 713-725. 1993.
16. Khan MA and Partin AW. Management of patients with an increasing prostate-specific antigen after radical prostatectomy. Curr Urol Rep. 5: 179-187. 2004.
17. Winkler MH, Khan FA, Hoh IM, Okeke AA, Sugiono M, McInerney P, Boustead GB,Persad R, Kaisary AV and Gillatt DA. Time trends in case selection, stage and prostate-specific antigen recurrence after radical prostatectomy: a multicentre audit. BJU Int. 93: 725-729. 2004.
18. Waselenko JK and Dawson NA.. Management of Progressive Metastatic Prostate Cancer. Oncology. 11: 1551-1560. 1997.
19. Bartsch G, Chi K, Cussenot O, Frenkel E, Gleave M, Klocker H, Logothetis C, Miyake H and Schlaken J. Innovative Approaches in Medical Management of Prostate Cancer: Other than Hormonal Therapies. In: Prostate Cancer. Denis L, Bartsch G, Khoury S, Murai M and Partin A (eds). Health Publications. pp. 161-216. Paris. 2003.
20. Analysenblätter der Firma Interlab Belp AG vom 28 Februar 2003 und des Steroid -Laboratoriums der Universität Bern vom 16. Dezember 2002 zum Ausschluss von Schwermetall – und Pestizidbelastung, sowie synthetischer Arzneimittel-Beimischung in Prostasol (personal communication).
21. Pfeifer B and Aeikens B. Komplementärmedizinische Therapien beim hormonrefraktären Prostatakarzinom – Phytotherapeutische und diätetische Ansätze. Onkologie. 1: 26-32. 2005.
22. Kratzer U and Pfeifer B. Clinical Evaluation of Prostasol – a new phytotherapeutic compound for prostate cancer. Annual Meeting Cancer Control Society. Abstract p. USA 2003.
23. von Holtz RL, Fink CS and Awad AB. Beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr Cancer. 32: 8-12. 1998.
24. Awad AB, Fink CS, Williams H and Kim U. In-vitro and in-vivo (SCID mice) effects of phytosterols on the growth and dissemination of human prostate cancer PC-3 cells. Eur J Cancer Pre. 10: 507-13. 2001.
25. Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K and Van Jaarsveld PP. Beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immune-modulatory vitamin combination. Int J Immunopharmacol. 18: 693-700. 1996.
26. Chan FL, Choi HL, Chen ZY, Chan PS and Huang Y. Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett. 160: 219-228. 2000.
27. Lichius JJ, Lenz C, Lindemann P, Muller HH, Aumuller G and Konrad L. Antiproliferative effect of a polysaccharide fraction of a 20% methanolic extract of stinging nettle roots upon epithelial cells of the human prostate (LNCaP). Pharmazie. 54: 768-771. 1999.
28. Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS and Ho CK. The anti-tumour effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer. 70: 699-705. 1997.
29. Knowles LM, Zigrossi DA, Tauber RA, Hightower C and Milner JA. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 38: 116-122. 2000.
30. Surh Y. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res. 428: 305-327. 1999.
31. Liu WK, Xu SX and Che CT. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sc. 67: 1297-1306. 2000.
32. Iguchi K, Okumura N, Usui S, Sajiki H, Hirota K and Hirano K. Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells. Prostate. 47: 59-65. 2001.
33. Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S and Howells. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene. 18: 6013-6020. 1999.
34. Verma SP, Salamone E and Goldin B. Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides. Biochemical and Biophysical Research Communications (USA). 233: 692-696. 1997.
35. Shenouda NS, Zhou C, Browning JD, Ansell PJ, Sakla MS, Lubahn DB and Macdonald RS. Phytoestrogens in common herbs regulate prostate cancer cell growth in-vitro. Nutr Cancer. 49: 200-208. 2004.
36. Dorai T, Dutcher JP, Dempster DW and Wiernik PH. Therapeutic potential of curcumin in prostate cancer – V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate. 60: 1-17. 2004.
37. Chaudhary LR and Hruska KA. Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells. J Cell Biochem. 89: 1-5. 2003.
38. Hour TC, Chen J, Huang CY, Guan JY, Lu SH and Pu YS. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappa B activation. Prostate. 51: 211-218. 2002.
39. Dorai T, Gehani N and Katz A. Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Mol Urol. 4: 1-6. 2000.
40. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R and Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 64: 353-356. 199.
41. Scifo C, Cardile V, Russo A, Consoli R, Vancheri C, Capasso F, Vanella A and Renis M. Resveratrol and propolis as necrosis or apoptosis inducers in human prostate carcinoma cells. Oncol Res. 14: 415-426. 2004.
42. Cardile V, Scifo C, Russo A, Falsaperla M, Morgia G, Motta M, Renis M, Imbriani E and Silvestre G. Involvement of HSP70 in resveratrol-induced apoptosis of human prostate cancer. Anticancer Res. 23: 4921-4926. 2003.
43. Gao S, Liu GZ and Wang Z. Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells. Prostat. 59: 214-25. 2004.
44. Awad AB, Burr AT and Fink CS. Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot Essent Fatty Acids. 72: 219-226. 2005.
45. Faucher K, Rabinovitch-Chable H, Barriere G, Cook-Moreau J and Rigaud M. Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges. Biochimie. 85: 611-617. 2003.
46. Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, Marshall JR, Clark LC. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 91: 608-612. 2003.
47. Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S and Rounder J. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol. 81: 730-734. 1998.
48. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL and Taylor JR. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 276: 1957-1963. 1996.
49. Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB and Giovannucci E. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst. 90: 1219-1224. 1998.
50. Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, Haapakoski J, Malila N, Rautalahti M, Ripatti S, Maenpaa H, Teerenhovi L, Koss L, Virolainen M and Edwards BK. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 90: 440-446. 1998.
51. Moyad MA. Selenium and vitamin E supplements for prostate cancer: evidence or embellishment? Urology. 59: 9-19. 2002.
52. Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR and Coltman C. SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design. Prostate Cancer Prostatic Dis. 3: 145-151. 2000.
53. Liao S. The medicinal action of androgens and green tea epigallocatechin gallate. Hong Kong Med J. 7: 369-374. 2001.
54. Adhami VM, Ahmad N and Mukhtar H. Molecular targets for green tea in prostate cancer prevention. J Nutr. 133: 2417S-2424S. 2003
55. Gupta S, Hussain T and Mukhtar H. Molecular pathway for epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch Biochem Biophys. 410: 177-185. 2003.
56. Gupta S, Ahmad N, Nieminen A and Mukhtar H. 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. Toxicol Appl Pharmacol. 164: 82-90. 2000.
57. Liao S, Umekita Y, Guo J, Kokontis JM and Hiipakka RA. Growth inhibition and regression of human prostate and breast tumours in athymic mice by tea epigallocatechin gallate. Cancer Lett. 96: 239-243. 1995.
58. Gupta S, Hastak K, Ahmad N, Lewin JS and Mukhtar H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci USA. 98: 10350-10355. 2001.
59. Kim L, Rao AV and Rao LG. Effect of Lycopene on Prostate LNCaP Cancer Cells in Culture. J Med Food. 5: 181-187. 2002.
60. Heber D and Lu QY. Overview of mechanisms of action of lycopene. Exp Biol Med (Maywood). 227: 920-923. 2002.
61. McNeel DG and Malkovsky M. Immune-based therapies for prostate cancer. Immunol Lett. 96: 3-9. 2005.
62. Pinthus JH, Waks T, Malina V, Kaufman-Francis K, Harmelin A, Aizenberg I, Kanety H, Ramon J and Eshhar Z. Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes. J Clin Invest. 114: 1774-1781. 2004.
63. Ragde H, Cavanagh WA and Tjoa BA. Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer. J Urol. 172: 2532-2538. 2004.
64. Ma Q, Safar M, Holmes E, Wang Y, Boynton AL and Junghans RP. Anti-prostate specific membrane antigen designer T cells for prostate cancer therapy. Prostate. 61: 12-25. 2004.
65. Rini B. Recent clinical development of dendritic cell-based immunotherapy for prostate cancer. Expert Opin Biol Ther. 4: 1729-34. 2004.
66. Ghoneum M and Abedi S. Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3/Biobran). J Pharm Pharmacol. 56: 1581-1588. 2004.
67. Ghoneum M and Matsuura M. Augmentation of macrophage phagocytosis by modified arabinoxylan rice bran (MGN-3/Biobran). Int J Immunopathol Pharmacol. 17: 283-292. 2004.
68. Ghoneum M, Jewett A. Production of tumour necrosis factor-alpha and interferon-gamma from human
peripheral blood lymphocytes by MGN-3, a modified arabinoxylan from rice bran, and its synergy with interleukin-2 in-vitro. Cancer Detect Prev. 24: 314-324. 2000.
69. Stoll G. Die Misteltherapie in der Onkologie. Z Onkol. 31: 31-34.1999.
70. Mansky PJ. Mistletoe and cancer: controversies and perspectives. Semin Oncol. 29: 589-594. 2002.
71. Heiny BM, Albrecht V and Beuth J. Lebensqualitätsstabilisierung durch Mistellektin-1-normierten Extrakt beim fortgeschrittenen kolorektalen Karzinom. Onkologe. 1: 35-39. 1998.
72. Lenartz D, Dott U, Menzel J and Beuth J. Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res. 20: 2073-2076. 2000.
73. Schmumacher K, Schneider B, Reich G, Stiefel T, Stoll G, Bock PR, Nanisch J and Beuth J. Postoperative komplementäre Therapie des primären Mammakarzinoms mit lektin-normiertem Mistelextrakt – eine epidemiologische, kontrollierte, multizentrische retrolektive Kohortenstudie. Dt Z Onkol. 34: 106-114. 2002.
74. Doll R and Peto R. The causes of cancer. Quantitative estimates of avoidable risks of cancer in the United States today. J Nat Cancer Inst. 66: 1193-1208. 1981.
75. Andersson SO, Wolk A, Bergstrom R, Adami HO, Engholm G, Englund A and Nyren O. Body size and prostate cancer: A 20-year follow-up study among 135,006 Swedish construction workers. J Natl Cancer Inst. 89: 385-389. 1997.
76. Kristal AR, Cohen JH, Qu P and Stanford JL. Associations of energy, fat, calcium and vitamin D with prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 11: 719-725. 2002.
77. Hursting SD, Thornquist M and Henderson MM. Types of dietary fat and the incidence of cancer at five sites. Prev Med. 19:242-253. 1990.
78. Berrigan D, Perkins SN, Haines DC and Hursting SD. Adult-onset calorie restriction and fasting delay spontaneous tumourigenesis in p53-deficient mice. Carcinogenesis. 23: 817-822. 2002.
79. Hsing AW, Tsao L and Devesa SS. International trends and patterns of prostate cancer incidence and mortality. Int J Cancer. 85: 60-7. 2000.
80. Denis L, Morton MS and Griffiths K. Diet and its preventive role in prostatic disease. Eur Urol. 35: 377-387. 1999.
81. Moyad MA. Dietary fat reduction to reduce prostate cancer risk: controlled enthusiasm, learning a lesson from breast or other cancers, and the big picture. Urology. 59: 51-62. 2002.
82. Hanash KA, Al-Othaimeen A, Kattan S, Lindstedt E, Al-Zahrani H, Merdad T, Peracha A, Kardar AH, Aslam M and Al-Akkad A. Prostatic carcinoma: a nutritional disease? Conflicting data from the Kingdom of Saudi Arabia. J Urol. 164: 1570-2. 2000.
83. Kolonel LN. Fat, meat and prostate cancer. Epidemiol Rev. 23: 72-81. 2001.
84. Michaud DS, Augustsson K, Rimm EB, Stampfer MJ, Willet WC and Giovannucci E. A prospective study on intake of animal products and risk of prostate cancer. Cancer Causes Control. 12: 557-67. 2001.
85. Bosland MC, Oakley-Girvan I and Whittemore AS. Dietary fat, calories and prostate cancer risk. J Natl Cancer Inst. 91: 489-91. 1999.
86. Ghosh J and Myers CE. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Natl Acad Sci USA. 27. 95: 13182-13187. 1998.
87. Chan JM, Giovannucci E, Andersson SO, Yuen J, Adami HO and Wolk A. Dairy products, calcium, phosphorous vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control. 9: 559-566. 1998.
88. Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW and Paffenbarger RS Jr. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 9: 795-804. 2000.


  1. No Article Comments available

Post Your Comments:

About Prof Ben L. Pfeifer MD PhD

Prof Ben L. Pfeifer MD PhD is Director for Clinical Research at Aeskulap Cancer Centre, Aeskulap Hospital, Brunnen, Switzerland. His specialities are Anaesthesiology, Intensive Care and Cancer Immunology. He is a widely published clinician, with 55 publications in peer reviewed medical journals, one book and 56 presented papers at national and international medical conferences. He has been an invited lecturer at the Academy of Sciences in Germany, Russia, USA and Poland. He has won honours, including the Humboldt-Prize and Immunological Research Prize, Florida, USA. He may be contacted via Professor Aeikens MD is a Professor of Urology. He is Director for Interventional Urology at Aeskulap Hospital.

  • Flower essences online

    Fine quality flower essences international ranges to help promote vitality and emotional well-being.

  • mycology research MRL

    MRL markets mushroom products food grade US & Netherlands GMP standards. Health Professional Videos

  • nutrition and cancer

    by Sandra Goodman PhD The latest scientific research regarding Nutrition and Cancer. Full details at

  • Super Patch Wellbeing

    Super Patches – a most revolutionary advance in wellbeing strategies in the history of medicine

  • Liposomal Nutrients

    Optimum system for nutrient delivery to cells - fully bioavailable vitamins absorbed and metabolised

top of the page