Combined Inhibitory Effects of Soy Isoflavones and Curcumin on the Production of Prostate-Specific Antigen

Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
The Prostate (Impact Factor: 3.57). 07/2010; 70(10):1127-33. DOI: 10.1002/pros.21147
Source: PubMed


Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. Since an elevated level of prostate-specific antigen (PSA) per se reflects the presence of inflammation in the prostate, intervention to improve the PSA value might potentially have beneficial effects for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti-inflammatory and anti-oxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP cells. After that, we conducted a clinical trial for men who received prostate biopsies, but were not found to have prostate cancer, to evaluate the effects of soy isoflavones and curcumin on serum PSA levels.
The expression of androgen receptor and PSA were examined in LNCaP cells before and after treatment of isoflavones and/or curcumin. Eighty-five participants were randomized to take a supplement containing isoflavones and curcumin or placebo daily in a double-blind study. Subjects were subdivided by the cut-off of their baseline PSA value at 10 microg/ml. We evaluated values of PSA before and 6 months after treatment.
The production of PSA were markedly decreased by the combined treatment of isoflavones and curcumin in prostate cancer cell line, LNCaP. The expression of the androgen receptor was also suppressed by the treatment. In clinical trials, PSA levels decreased in the patients group with PSA >or= 10 treated with supplement containing isoflavones and curcumin (P = 0.01).
Our results indicated that isoflavones and curcumin could modulate serum PSA levels. Curcumin presumably synergizes with isoflavones to suppress PSA production in prostate cells through the anti-androgen effects.

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    • "Isoflavones contained 66% daidzein, 24% glycitein, and 10% genistein. PSA levels were significantly decreased in the supplement-treated subgroup compared with the placebo group only in those subjects whose baseline PSA levels were over 10 ng/ml [33]. "
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    ABSTRACT: The burden of increasing morbidity and mortality due to prostate cancer imposes a need for new, effective measures of prevention in daily life. The influence of lifestyle on carcinogenesis in Asian men who migrate to Western cultures supports a causal role for dietary, environmental, and genetic factors in the epidemiology of prostate cancer. Chemoprevention, a prophylactic approach that uses nontoxic natural or synthetic compounds to reverse, inhibit, or prevent cancer by targeting specific steps in the carcinogenic pathway, is gaining traction among health care practitioners. Soy isoflavones and curcumin, staples of the Asian diet, have shown promise as functional factors for the chemoprevention of prostate cancer because of their ability to modulate multiple intracellular signaling pathways, including cellular proliferation, apoptosis, inflammation, and androgen receptor signaling. Recent evidence has revealed the DNA damage response (DDR) to be one of the earliest events in the multistep progression of human epithelial carcinomas to invasive malignancy. Soy isoflavones and curcumin activate the DDR, providing an opportunity and rationale for the clinical application of these nutraceuticals in the chemoprevention of prostate cancer.
    Full-text · Article · Oct 2012 · Korean journal of urology
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    • "Curcumin, a curcuminoid, and genistein, an isoflavone, are derived from two different chemical classes, yet they have been known to inhibit a variety of tumor types in vitro and in vivo. Clinical trials of these compounds individually have been tested [19, 60, 104, 105]. The mechanistic action of the individual compounds in many different cancers has been investigated as well. "
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    ABSTRACT: The genesis of cancer is often a slow process and the risk of developing cancer increases with age. Altering a diet that includes consumption of beneficial phytochemicals can influence the balance and availability of dietary chemopreventive agents. In chemopreventive approaches, foods containing chemicals that have anticancer properties can be supplemented in diets to prevent precancerous lesions from occurring. This necessitates further understanding of how phytochemicals can potently maintain healthy cells. Fortunately there is a plethora of plant-based phytochemicals although few of them are well studied in terms of their application as cancer chemopreventive and therapeutic agents. In this analysis we will examine phytochemicals that have strong chemopreventive and therapeutic properties in vitro as well as the design and modification of these bioactive compounds for preclinical and clinical applications. The increasing potential of combinational approaches using more than one bioactive dietary compound in chemoprevention or cancer therapy will also be evaluated. Many novel approaches to cancer prevention are on the horizon, several of which are showing great promise in saving lives in a cost-effective manner.
    Full-text · Article · Jan 2012 · Journal of Oncology
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    • "Several studies have indicated that PSA is a molecular target of curcumin in the prostate. The function of curcumin is to enhance AR degradation that blocks AR activation and downregulated PSA expression in vitro and in vivo [6] [7] [35]. One previous study indicated that treatment of prostate carcinoma PC3 cells with curcumin or EF24, a novel curcumin analog, led to the inhibition of HIF-1a protein levels and, consequently, inhibition of HIF transcriptional activity [36]. "
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    ABSTRACT: Prostate-specific antigen (PSA) is a well-known marker for diagnosing and monitoring prostate cancer. Curcumin, a yellow curry pigment, has been reported to enhance androgen receptor (AR) degradation. We examined the effects of curcumin on increasing PSA expression by hypoxia and prolyl hydroxylase inhibitors, L-mimosine and dimethyloxalylglycine (DMOG), in human prostate carcinoma LNCaP cells. The 3H-thymidine incorporation assay revealed that either L-mimosine or DMOG treatments attenuated cell proliferation. Immunoblot and enzyme-linked immunosorbent assays (ELISA) indicated that both L-mimosine and DMOG have an effect similar to hypoxia, which stabilized hypoxia-inducible factor-1α (HIF-1α) and induced PSA gene expression. The results of the immunoblot and transient gene expression assays indicated that induction of the PSA expression by hypoxia is both HIF-1α- and AR-dependent. Immunoblot assays revealed that a curcumin treatment (10 μM) decreased the protein abundance of AR but did not significantly affect the protein levels of HIF-1α and vascular endothelial growth factor, which were induced by hypoxia. ELISA and transient gene expression assays indicated that curcumin blocked the activation of L-mimosine or DMOG treatment on PSA expression. These results indicate that curcumin blocked the enhanced effect of PSA expression by L-mimosine and DMOG that induce hypoxia condition.
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