Resveratrol induces apoptosis of bladder cancer cells via miR-21 regulation of the Akt/Bcl-2 signaling pathway

Abstract

Abstract. Resveratrol, an edible polyphenolic phytoalexin present in grapes and red wine, has been reported to inhibit proliferation and induce apoptosis of bladder cancer cells. In the present study, the molecular mechanisms of resveratrol on human bladder cancer cell apoptosis was examined. The effect of resveratrol on the viability and apoptosis of T24 and 5637 cells was measured using an MTT assay and flow cytometric analysis, respectively. Next, the effect of resveratrol on miR-21 expression was detected by real-time PCR. The expression of phospho-Akt and Bcl-2 following treatment with resveratrol or the downregulation of miR-21 expression were also measured. Resveratrol induced the cytotoxicity and apoptosis of T24 and 5637 cells in a dose-dependent manner. Resveratrol decreased the expression of miR-21, the level of phospho-Akt and Bcl-2 protein expression. In addition, the downregulation of miR-21 expression inhibited the level of phospho-Akt and Bcl-2 expression. Insulin-like growth factor-1 was able to reverse the effect of the miR-21 inhibitor on Bcl-2 expression and apoptosis in T24 and 5637 cells. Notably, overexpression of miR-21 expression was able to restore the inhibition of Akt activity, downregulation of Bcl-2 expression and apoptosis induced by resveratrol. Collectively, data revealed that the effect of resveratrol on bladder cancer cell apoptosis was due to miR-21 regulation of the Akt/Bcl-2 signaling pathway.

Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells

“…However, by up-regulation of Bcl2 and inhibition of p53 and Bax, RES reverses cadmium chloride-induced testicular damage and subfertility [79]. In bladder cancer cells, RES also induces apoptosis by down-regulating the expression of Bcl2 proteins [81, 82]. However, the current results show that RES modulates the expression of Bax and Bcl2 in TRAMP-C1, TRAMP-C2, and TRAMP-C3 cells compared to the control cells; however, in TRAMP-C1 cells Bax at 50 μM of RES and Bcl2 at 50 μM and 100 μM of RES were found insignificant.…”

Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

“…RSV induced apoptosis in several cancer cells such as human colorectal and bladder cancers. This effect was through activation of caspase and regulation of the Akt/Bcl-2 signaling pathway [30, 31]. RSV sensitized colon cancer cell lines to 5-fluorouracil treatment on the increase of apoptotic effect and exhibited stronger antitumor effect [32].…”

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

“…While inducing apoptosis resveratrol decreased the miR-21 level, and subsequently the phosphorylated AKT and BCL2 protein levels in human pancreatic cancer cells (PANC-1, CFPAC-1 and MIA Paca-2), as described in [505, 506]. Based on microRNA microarray studies, resveratrol was found to reduce the expression of various prostate-tumor associated microRNAs, including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells (PC-3M-MM2), as described elsewhere [507].…”

“…Resveratrol induced the cytotoxicity and apoptosis of human bladder cancer cells (T24 and 5637 cells) in a dose-dependent manner [505]. While inducing apoptosis resveratrol decreased the miR-21 level, and subsequently the phosphorylated AKT and BCL2 protein levels in human pancreatic cancer cells (PANC-1, CFPAC-1 and MIA Paca-2), as described in [505, 506].…”