prostate

Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients.: Support Care Cancer. 2007 Aug;15(8):913-21 Authors: Walji R, Boon H, Guns E, Oneschuk D, Younus J

GOALS OF WORK: Black cohosh is commonly used to treat hot flashes and other symptoms associated with menopause. It is thought to have multiple mechanisms of action, including potential phytoestrogenic properties. This has caused some concern about its use by patients with hormone-sensitive cancer. This paper will present the results of a systematic review of the safety and efficacy of black cohosh (Cimicifuga racemosa [L.] Nutt.) in patients with cancer. MATERIALS AND METHODS: A critical assessment of clinical (n = 5) and preclinical (n = 21) studies of black cohosh and cancer (breast and prostate) to treat hot flashes and other related symptoms is presented. In addition, clinical studies, case reports, animal studies, and in vitro assessments of the safety of black cohosh for patients with hormonally sensitive cancers is summarized and interpreted. MAIN RESULTS: In general, the research assessing efficacy of black cohosh for the treatment of hot flashes in women with breast cancer is inconclusive. There is laboratory evidence of antiproliferative properties but no confirmation from clinical studies for a protective role in cancer prevention. Black cohosh seems to have a relatively good safety profile. Concerns about liver toxicity are inconclusive. With relevance to cancer patients, black cohosh also seems not to exhibit phytoestrogenic activity and is in fact possibly an inhibitor of tumor growth. CONCLUSIONS: The use of black cohosh appears to be safe in breast cancer patients without risk for liver disease, although further research is needed in this and other populations.

PMID: 17602247 [PubMed - indexed for MEDLINE]

A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix.: Phytomedicine. 2007 Aug;14(7-8):568-79 Authors: Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik S

Nettle root is recommended for complaints associated with benign prostatic hyperplasia (BPH). We therefore conducted a comprehensive review of the literature to summarise the pharmacological and clinical effects of this plant material. Only a few components of the active principle have been identified and the mechanism of action is still unclear. It seems likely that sex hormone binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid membrane receptors are involved in the anti-prostatic effect, but less likely that 5alpha-reductase or androgen receptors are involved. Extract and a polysaccharide fraction were shown to exert anti-inflammatory activity. A proprietary methanolic nettle root extract and particular fractions inhibited cell proliferation. Isolated lectins (UDA) were shown to be promising immunomodulatory agents, having also anti-viral and fungistatic effects. However, despite these in vitro studies it is unclear whether the in-vitro or animal data are a surrogate for clinical effects. The clinical evidence of effectiveness for nettle root in the treatment of BPH is based on many open studies. A small number of randomised controlled studies indicate that a proprietary methanolic extract is effective in improving BPH complaints. However, the significance and magnitude of the effect remains to be established in further confirmatory studies before nettle root treatment may be accepted in the guidelines for BPH treatment. The risk for adverse events during nettle root treatment is very low, as is its toxicity. Pre-clinical safety data remain to be completed.

PMID: 17509841 [PubMed - indexed for MEDLINE]

Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection.: Arch Ital Urol Androl. 2007 Jun;79(2):84-92 Authors: Magri V, Trinchieri A, Montanari E, Del Nero A, Mangiarotti B, Zirpoli P, de Eguileor M, Marras E, Ceriani I, Vral A, Perletti G

We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was calculated in patients affected by cat. II, IIIa, IIIb and IV prostatitis after stratification with respect to the concomitant presence or absence of benign prostatic hyperplasia (BPH). PSA was reduced by 41% in cat. II CBP patients without BPH, compared to a 12.7% reduction in patients affected by BPH. Cat. IIIa CP/CPPS patients without BPH showed a 58.3% reduction of PSA levels, compared to a 20.7% reduction observed in CPPS/BPH patients. These data show that the presence of BPH may prevent the reduction of PSA induced by combination pharmacological therapy, and suggest that care has to be taken in the adoption of PSA as a marker of therapeutic efficacy in the presence of confounding factors like BPH. PSA should in our opinion be used as a significant component of a strategy integrating multiple diagnostic approaches.

PMID: 17695414 [PubMed - indexed for MEDLINE]

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.: Phytomedicine. 2007 Aug;14(7-8):460-4 Authors: Gasco M, Villegas L, Yucra S, Rubio J, Gonzales GF

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

PMID: 17289361 [PubMed - indexed for MEDLINE]

[Effects of phytoestrogens on prostate cancer and benign prostatic hyperplasia]: Zhonghua Nan Ke Xue. 2007 May;13(5):457-61 Authors: Feng Y, Xia XY, Huang YF

Phytoestrogens are non-steroidal estrogens widely distributed in many kinds of plants. They are natural compounds structurally similar to estrogen and with estrogenic or anti-androgenic activities. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent and associated with age. Recently, in many epidemiological and experimental researches, it has been reported that phytoestrogens play a role in the prevention and treatment of PCa and BPH. Regulation of sexual hormones, inhibition of cell proliferation, induction of cell apoptosis and anti-oxidation of such plant estrogens may be involved in the mechanisms.

PMID: 17569267 [PubMed - in process]

Traditional chinese medicine for the treatment of chronic prostatitis in China: a systematic review and meta-analysis.: J Altern Complement Med. 2006 Oct;12(8):763-9 Authors: Chen JX, Hu LS

OBJECTIVE: To systematically evaluate the effectiveness of Chinese herbal medicine for treating chronic prostatitis (CPT) in China. DESIGN: Electronic medical database from China National Knowledge Infrastructure (CNKI) was searched, language is Chinese; date is from January 1, 1994 to December 31, 2003. A total of 108 trials were found, and all studies with words like "randomization" or "quasi-randomization" in their abstracts were included, whether they used blinding or not. Nineteen theses that met the entry criteria were downloaded and fully printed. Four groups were divided: Chinese herbs orally treated group (based on syndrome differentiation), Chinese herbs externally treated group, Chinese herbs orally and externally treated group, and integrated Western with Chinese herbs treated group. RESULTS: All 19 articles that met the entry criteria were clinical trial studies with low quality (Jadad Score <3). The results showed that Traditional Chinese Medicine (TCM) may benefit the patients who had CPT. However, from the results of the funnel plots analysis of all four groups of clinical trials that met the inclusion criteria in this systematic review are distant asymmetrical and irregular plots, which indicate that a positive publication bias may exist. There was no obvious evidence indicating that the efficacy of the therapy in the treated groups using TCM was superior to that of the control group (Western medicine treatment group). CONCLUSIONS: All of the four groups in the clinical trials have not provided evidence of evidence-based medicine (EBM) A class (including 1a, 1b, 1c level), failed to prove that the TCM may have beneficial effects for patients with CPT, because of low quality in all the trials and a positive publication bias. Therefore, in light of some positive outcomes, a good design of multicentered, randomized, parallel-controlled and blinding trials is needed in order to make further studies, and deserve further examination for the treatment of CPT with TCM.

Garlic phytoestrogen compounds can protect bone loss in patients with prostate cancer under androgen deprivation.: Med Sci Monit. 2007 Jan 18;13(2):BR25-31 Authors: Kream RM, Liu NJ, Zhuang M, Esposito PL, Esposito TR, Stefano GB, Witmeyer Iii JJ

Background: We have previously explored the functional role of the tachykinin substance P (SP) in the mediation of opioid-dependent antinociception and now describe the formulation, synthesis, and initial pharmacological characterization of a hybrid chimeric molecule, designated MSP9, containing the mu opioid receptor (MOR) agonist morphine covalently attached through a succinic acid linker to the SP receptor (SPR) agonist domain SP3-11. Material/Methods: Pharmacological characterization of MSP9, administered by the intramuscular route, was achieved in naive and morphine-tolerant male rats utilizing the tail-flick test. Results: MSP9 produced significant antinociceptive responses across a wide concentration range and displayed an atypical bell-shaped analgesic dose response relationship with peak effect of 40+/-10% reached at 0.2 mg/kg. The antinociceptive responses achieved by very low concentrations of MSP9 were not obtained by administration of equivalent low doses of morphine, suggesting that kinetic and dynamic parameters may contribute to its unusual analgesic properties. Importantly, MSP9 produces a strong antinociceptive response when administered to morphine-tolerant rats, suggesting a significant activation of kappa and/or delta receptors (KORs and DORs, respectively) in the presence of functionally down regulated MORs. Conclusions: Analyses employing selective, blood brain barrier (BBB) permeable, opioid and SP antagonists administered alone or in combination, indicate an obligate requirement for coincident activation of populations of CNS opioid and SP receptors. These combined data suggest that MSP9 activates multiple opioid- and SPR-expressing systems functionally linked to CNS analgesic responses, designating this class of hybrid chimeric molecules as prime candidates for therapeutic development for a wide range of clinical indications.

Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray.: Mol Carcinog. 2006 Dec;45(12):943-56 Authors: Takahashi Y, Lavigne JA, Hursting SD, Chandramouli GV, Perkins SN, Kim YS, Wang TT

The present study utilized microarray technology as a tool to elucidate the molecular signatures of soy-derived phytochemicals in the human androgen-responsive prostate cancer cell line LNCaP. Global gene expression pattern analysis of LNCaP cells exposed to 0, 1, 5, or 25 microM of the soy-derived phytochemicals equol and daidzein were conducted and compared. The data were further compared with previously generated data from exposure of LNCaP cells to the same doses of genistein, a soy isoflavone. Multidimensional scaling (MDS) analyses of the expression patterns suggest that these compounds exerted differential effects on gene expression in LNCaP cells. Further examination of specific gene changes revealed that these compounds differentially modulated genes in multiple cellular pathways, including the cell-cycle pathway genes. However, the three compounds also exerted similar effect on genes belonging to several other important cellular pathways. A universal effect of the three compounds on androgen-responsive genes, IGF-1 pathway gene, and MAP kinase-related pathway gene was observed. These results provide the foundation for establishing molecular signatures for equol, daidzein, and genistein. Moreover, these results also allow for the identification of candidate mechanism(s) by which soy phytochemicals and soy may act in prostate cancer cells.

Saw palmetto supplement use and prostate cancer risk.: Nutr Cancer. 2006;55(1):21-7 Authors: Bonnar-Pizzorno RM, Littman AJ, Kestin M, White E

Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.

Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts.: >BJU Int. 2006 Nov;98(5):1106-13 Authors: Boulbès D, Soustelle L, Costa P, Haddoum M, Bali JP, Hollande F, Magous R

OBJECTIVE: To investigate the effect of Pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts; this extract is used for treating urinary disorders associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU) incorporation assays, and cytotoxicity by luminescent quantification of adenylate kinase activity. RESULTS: Cultured cells were labelled by an anti-vimentin antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed that proliferation of cultured human stromal cells, stimulated by fetal calf serum, by basic fibroblast growth factor and by epidermal growth factor, was dose-dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL, no acute cytotoxicity of the extract was detected after 24 h of culture. Similarly, the extract dose-dependently inhibited the proliferation of Madin-Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose of extract, no acute toxicity was evident on this cell line. CONCLUSION: PA extract inhibits the proliferation of cultured human prostatic myofibroblasts and fibroblasts. We propose that cultured human prostatic cells offer a reliable model for preclinical screening of therapeutic agents, and to study the mechanisms underlying the inhibition of proliferation.