TY - JOUR TI - Disulfiram-copper activates chloride currents and induces apoptosis with tyrosine kinase in prostate cancer cells AU - Lei, Wei AU - Xu, Jingkui AU - Ya, Yiyao AU - Zhang, Jinxiang AU - Hou, Xiuying AU - Zhai, Qiliang AU - Zha, Zeyu AU - Zhuo, Yangjia AU - Zhou, You AU - Yuan, Hong AU - Liang, Yuxiang AU - Han, Zhaodong AU - Zhong, Weide AU - Zhu, Linyan AU - Chen, Yehui T2 - Asia-Pacific Journal of Clinical Oncology AB - Aim: To elucidates the mechanism that disulfiram/copper complex (DSF/Cu) treatment activates chloride channels and induces apoptosis in prostate cancer cells. Methods: Cellular membrane currents were measured by membrane clamp technique; western blot to detect protein expression; flow cytometry to detect apoptosis; immunofluorescence to detect target protein co-localization, and further validated by a combination of protein-protein interaction and mock protein molecular docking techniques. Results: DSF/Cu activated chloride channels and induced apoptosis in LNCaP (a type of androgen-dependent prostate cancer cells) cells. The chloride currents activated by DSF/Cu were significantly reduced after knockdown of CLC3 with siRNA. In addition, DSF/Cu-activated chloride currents were reduced to background current levels after perfusion with genistein, a highly specific tyrosine kinase inhibitor. Conversely, DSF/Cu failed to activate chloride currents in LNCaP cells after 30 minutes of pre-incubation with genistein. When genistein was removed, and DSF/Cu was added, the activated currents were small and unstable, and gradually decreased. Immunofluorescence in LNCaP cells also showed co-localization of the CLC3 protein with tyrosine kinase 2β (PTK2B). Conclusion: DSF/Cu can activate chloride channels and induce apoptosis in LNCaP cells with the involvement of tyrosine kinase. These results provide new insights into the target therapy of prostate cancer. DO - https://doi.org/10.1111/ajco.13551 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1743-7563 UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/ajco.13551 Y2 - 2021/02/26/16:52:09 KW - DSF/Cu KW - apoptosis KW - chloride channels KW - prostate cancer KW - tyrosine kinase ER -