Polydatin exerts anti-tumor effects against renal cell carcinoma cells via induction of caspase-dependent apoptosis and inhibition of the PI3K/Akt pathway

Yi-Li Jin,1 Li-Min Xin,2 Chang-Chun Zhou,1 Yu Ren2 1Department of Urology, Dongyang People’s Hospital, Wenzhou Medical University, Dongyang, Zhejiang 322100, People’s Republic of China; 2Laboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, People’s Republic of China Purpose: Polydatin, a stilbenoid glucoside of a resveratrol derivative, has many biological functions, including antitumor effects. However, the antitumor effects of polydatin in renal cell carcinoma (RCC) have not been investigated. Materials and methods: In the current study, MTT assays, transwell invasion assays and wound healing assays were performed to examine cell proliferation, invasion and migration. An apoptosis nucleosome ELISA was used to measure apoptosis. Caspase activity assays were applied to measure the activities of caspase-3/9. A Western blot assay was used to measure the change in protein levels. Results: Our data demonstrated that polydatin inhibited the proliferation of RCC cells but not normal renal epithelial cells in a time- and dose-dependent manner. Polydatin also triggered apoptosis in a caspase-dependent manner. Moreover, polydatin treatment also led to the downregulation of Bcl-2 and Mcl-1 and to activation of Bax. Ectopic expression of Bcl-2 and Mcl-1 or silencing of Bax could repress the apoptosis that was induced by polydatin. Moreover, incubation with polydatin also suppressed the PI3K/Akt signaling pathway in RCC cells. Conclusion: Taken together, our data indicated that polydatin may be applied as a potent agent against RCC. Keywords: polydatin, renal cell carcinoma, apoptosis, PI3K, Akt