Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV‐40 tag rats

Abstract

Background Chemoprevention utilizing dietary agents is an effective means to slow the development of prostate cancer. We evaluated the potential additive and synergistic effects of genistein and resveratrol for suppressing prostate cancer in the Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model, a transgenic model of spontaneously developing prostate cancer. Methods Rats were fed genistein or resveratrol (250 mg/kg AIN-76A diet) alone and in combination, and a low dose combination (83 mg genistein + 83 mg resveratrol/kg diet). Histopathology and mechanisms of action studies were conducted at 30 and 12 weeks of age, respectively. Results Genistein, resveratrol, and the high dose combination treatments suppressed prostate cancer. The low dose combination did not elicit protection against prostate cancer and was most likely below the effective dose for causing significant histopathological changes. Total genistein and resveratrol concentrations in the blood reached 2160 and 211 nM, respectively in rats exposed to the single treatments. Polyphenol treatments decreased cell proliferation and insulin-like growth factor-1 (IGF-1) protein expression in the prostate. In addition, genistein as a single agent induced apoptosis and decreased steroid receptor coactivator-3 (SRC-3) in the ventral prostate (VP). Conclusions Genistein and resveratrol, alone and in combination, suppress prostate cancer development in the SV-40 Tag model. Regulation of SRC-3 and growth factor signaling proteins are consistent with these nutritional polyphenols reducing cell proliferation and increasing apoptosis in the prostate.

Inhibitory mechanisms of the transcriptional activity of androgen receptor by resveratrol: Implication of DNA binding and acetylation of the receptor

“…Because androgen-dependent AR function plays a pivotal role in the development of prostate cancer, AR is recognized as a preventative and therapeutic target for prostate cancer [9]. Resveratrol inhibits the prostate cancer cells in vitro and suppresses the progression of prostate cancer in in vivo mouse and rat adenocarcinoma models [12,16,27,28]. In the present study, we identified the mechanism by which resveratrol inhibits the transcriptional activity of AR.…”

Pterostilbene Inhibits Pancreatic Cancer In Vitro

“…Resveratrol, a stilbene found in grapes, has been shown to inhibit a variety of primary tumors. [5][6][7][8][9] Pterostilbene, an analogue of resveratrol found in blueberries, has been shown to inhibit gastric, colon, and breast cancer as well as leukemia and melanoma in various in vitro and animal model systems. [10][11][12][13][14][15] Furthermore, its molecular structure makes it substantially more bioavailable than resveratrol upon oral ingestion.…”

SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 destabilization

“…A high SRC-3 protein level also correlates with resistance to EGFR antagonists in lung cancers (Cai et al 2010). On the other hand, downregulation of the SRC-3 protein level is considered an important step for enhancing the ability of several anticancer agents to effectively combat cancers (Harper et al 2009;Li et al 2009a,b). Thus, the expression level of SRC-3 may be an important factor in controlling the responses of cancer cells to anti-cancer therapies.…”