Disulfiram‐copper activates chloride currents and induces apoptosis with tyrosine kinase in prostate cancer cells.

Autor: Lei, Wei, Xu, Jingkui, Ya, Yiyao, Zhang, Jinxiang, Hou, Xiuying, Zhai, Qiliang, Zha, Zeyu, Zhuo, Yangjia, Zhou, You, Yuan, Hong, Liang, Yuxiang, Han, Zhaodong, Zhong, Weide, Zhu, Linyan, Chen, Yehui
Předmět:
Zdroj: Asia Pacific Journal of Clinical Oncology; Apr2022, Vol. 18 Issue 2, pe46-e55, 10p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje