Effects of a High Dose, Aglycone-Rich Soy Extract on Prostate-Specific Antigen and Serum Isoflavone Concentrations in Men With Localized Prostate Cancer

University of California, Davis, Sacramento, California 95616, USA.
Nutrition and Cancer (Impact Factor: 2.32). 11/2010; 62(8):1036-43. DOI: 10.1080/01635581.2010.492085
Source: PubMed

ABSTRACT The efficacy and safety of consuming high-dose isoflavone supplements for prostate cancer is not clear. A double-blind, placebo controlled, randomized trial was conducted in 53 men with prostate cancer enrolled in an active surveillance program. The treatment group consumed a supplement containing 450 mg genistein, 300 mg daidzein, and other isoflavones daily for 6 mo. Prostate-specific antigen (PSA) was measured in both groups at baseline, 3 mo, and 6 mo, and serum concentrations of genistein, daidzein, and equol were assessed at baseline and 6 mo in the treatment group. Following the completion of the 6-mo double-blind study, men were enrolled in a 6-mo open label trial with the same isoflavone-rich supplement, and PSA was measured at 3 and 6 mo. PSA concentrations did not change in either group after 6 mo or after 12 mo when the open-label study was included. The 6 mo serum concentrations of genistein and daidzein (39.85 and 45.59 μmol/l, respectively) were significantly greater than baseline values and substantially higher than levels previously reported in other studies. Equol levels did not change. Although high amounts of aglycone isoflavones may result in significantly elevated serum concentrations of genistein and daidzein, these dietary supplements alone did not lower PSA levels in men with low-volume prostate cancer.

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Available from: Robert M. Hackman, Nov 04, 2014
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    • "Genistein induces the transcription of antiangiogenic and anti-metastatic genes, as well as increases cell adhesion by stimulating the focal adhesion kinase pathway in PCa cells [169] [170]. Genistein is available in the market and it has been tested in clinical trials, although the results were not the most favourable [171]. Other phytoestrogens have been listed as PCa protectors, mostly by eliciting apoptosis and inhibiting proliferation [77] [172] [173] [174]. "
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    ABSTRACT: Although the most impressive characteristic of prostate cancer is its androgen dependence, several studies support that 17β-estradiol (E2) also play an important role in onset and progression of prostate cancer. Regarding the effects of E2 in prostate carcinogenesis, we can highlight the carcinogenic properties of several products derived from E2 metabolism, which play an important role on cell malignant transformation. Several polymorphisms in estrogen-related genes such as estrogen receptors (ERs) and enzymes involved in E2 biosynthesis and metabolism have been described to favour carcinogenesis. Also, both isoforms of ERs (ERα and ERβ), which act on cells in order to maintain the normal physiology of prostate gland, are differentially expressed between neoplastic and non-neoplastic prostate cells. Therefore, this deregulation may conduct to alterations on normal gene expression in prostate cells, which may favour the progression and migration of cancer cells. On the other hand, other studies have been pointing the anti-carcinogenic activity of E2 in prostate. These contradictory effects are based on the role of ERβ, which has been shown to exhibit anti-proliferative and anti-oxidant functions. Taking into account the scientific evidences that relate E2 with prostate cancer, several therapeutic approaches based on ERs are being explored. This chapter summarizes the main knowledge on how E2 may contribute to the pathophysiology of prostate gland
    Estradiol: synthesis, Health Effects and Drug Interactions, 01/2013: chapter Estrogens and prostate cancer: from biosynthesis to physiological effects; , ISBN: ISBN: 978-1-62808-962-2
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    • "A case–control study in white subjects who consumed a Western diet reported slight protective effects of genistein consumption against prostate cancer (Strom et al. 1999). Highly purified genistein and daidzein are available; they have already been tested in a small double-blinded, placebo-controlled study for localized prostate cancer (deVere White et al. 2010), though with negative results. Genistein and daidzein inhibit the proliferation of different types of cancer cells (Peterson and Barnes 1991, 1993; Zhou et al. 1999), 3T3 cells (Linassier et al. 1990), and normal colonic mucosa (Majumdar 1990), in tissue culture. "
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    ABSTRACT: Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.
    European Journal of Drug Metabolism and Pharmacokinetics 11/2012; 38(1). DOI:10.1007/s13318-012-0112-y · 1.56 Impact Factor
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    • "Next, we investigated which components of GCP are responsible for its effects. In human patients, the serum levels of genistein and daidzein were determined to be 43 and 51 ×… mol/L respectively (about 10 ×… g/ml each in an average adult male), following 6 months of GCP intake at 5g/day (deVere White et al. 2010). At comparable doses, daidzein reduced proliferation in the absence, rather than the presence, of androgens (22.4% decrease in FBS, p=0.039, vs. 69.5% decrease in CSS, p<0.0001) whereas the effect of genistein remained virtually unchanged in FBS (84.68% decrease, p=0.002) vs CSS (74% decrease, p<0.0001) (Figure 4A). "
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    ABSTRACT: Since prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280kDa structural protein Filamin A (FlnA) to a 90kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT. Hence, treatment promoting FlnA nuclear localization would enhance androgen responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in CRPC cells during ADT, identifying it as a treatment tool in advanced CaP. Significantly, the natural product genistein-combined-polysaccharide (GCP) had a similar effect. Investigation of the mechanism of GCP-induced apoptosis showed that GCP induced FlnA cleavage and nuclear localization, and that apoptosis resulting from GCP treatment was mediated by FlnA nuclear localization. Two main components of GCP are genistein and daidzein: the ability of GCP to induce G2 arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein; hence both were needed to mediate GCP's effects. FlnA cleavage is regulated by its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not vehicle, impeded relapse following castration; indicating that GCP, when administered with ADT, interrupted the development of CRPC. These results demonstrate the efficacy of GCP in promoting FlnA nuclear localization and enhancing androgen responsiveness in CaP.
    Endocrine Related Cancer 09/2012; 19(6). DOI:10.1530/ERC-12-0171 · 4.81 Impact Factor
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