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Stomping out prostate cancer

Several seminal studies have demonstrated the beneficial effects of the NAD-dependent histone deacetylase SIRT1 activator, resveratrol, in preventing cardiovascular diseases and cancer. Although SIRT1 possesses both tumorigenic and anti-tumorigenic potential, the molecular mechanisms underlying SIRT1-mediated tumor progression or regression are still poorly understood.

In a recent study published in Cancer Prevention Research, Dr. Li and coworkers from the University of Texas in San Antonio investigated the effect of resveratrol on multiple human prostate cancer cell lines and a prostate-specific PTEN-knockout mouse model. They found that androgen-independent prostate cancer cell lines expressed higher levels of SIRT1 than androgen-responsive and non-tumorigenic prostate cells. Resveratrol was shown to enhance SIRT1 expression without any significant effect on its enzymatic activity as measured with Enzo’s Fluor-de-Lys® SIRT1 fluorometric drug discovery assay kit. Stable knockdown of SIRT1 expression significantly enhanced cell proliferation and inhibited autophagy as demonstrated with Enzo’s Cyto-ID® Autophagy detection kit. These effects were reversed following treatment with resveratrol through phosphorylation of S6K and 4E-BP1. Consistent with the in vitro findings, prostate tissue from PTEN-knockout mice given a resveratrol diet were analyzed and showed a significant reduction in prostate weight and in the incidence of high-grade prostatic intra-epithelial neoplastic lesions by approximately 54%. Interestingly, resveratrol intervention was associated with reduced prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1. Altogether, these data suggest that SIRT1/S6K-mediated inhibition of autophagy drives prostate tumorigenesis and that modulation of SIRT1/S6K signaling may offer an effective therapeutic strategy against prostate cancer.

Enzo Life Sciences offers a comprehensive portfolio of epigenetic drug discovery tools, some of which are described below:

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References:

  • G. Li, et al. Dietary Resveratrol Prevents Development of High-Grade Prostatic Intra-epithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis. Cancer Prev. Res. (2013) 6: 27.

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