Benzyl isothiocyanate induces reactive oxygen species-initiated autophagy and apoptosis in human prostate cancer cells
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Ji-Fan Lin1,*, Te-Fu Tsai2,3,*, Shan-Che Yang1, Yi-Chia Lin2, Hung-En Chen2, Kuang-Yu Chou2,3, Thomas I-Sheng Hwang2,3,4
1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan
2Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan
3Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, 242, Taiwan
4Department of Urology, Taipei Medical University, Taipei, 111, Taiwan
*These authors have contributed equally to this work
Thomas I-Sheng Hwang, email: [email protected]
Keywords: benzyl isothiocyanate, reactive oxygen species, apoptosis, autophagy, prostate cancer
Received: December 25, 2015 Accepted: December 03, 2016 Published: February 23, 2017
Benzyl isothiocyanate (BITC) in cruciferous plants, which are part of the human diet, has been shown to induce apoptosis in various types of cancer. In this study, we show that BITC effectively suppresses the growth of cultured human prostate cancer cells (CRW-22Rv1 and PC3) by causing mitochondrial membrane potential loss, caspase 3/7 activation and DNA fragmentation. Furthermore, BITC induces ROS generation in these cells. The induction of apoptosis by BITC was significantly attenuated in the presence of N-acetylcysteine (NAC) and catalase (CAT), well-studied ROS scavengers. The induction of autophagy in BITC-treated cells were also diminished by the application of NAC or CAT. In addition, BITC-induced apoptosis and autophagy were both enhanced by the pretreatment of catalase inhibitor, 3-Amino-1,2,4-triazole (3-AT). Pretreatment with specific inhibitors of autophagy (3-methyladenine or bafilomycin A1) or apoptosis (Z-VAD-FMK) reduced BITC-induced autophagy and apoptosis, respectively, but did not abolish BITC-induced ROS generation. In conclusion, the present study provides evidences that BITC caused prostate cancer cell death was dependent on the ROS status, and clarified the mechanism underlying BITC-induced cell death, which involves the induction of ROS production, autophagy and apoptosis, and the relationship between these three important processes.
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