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

Autor: Lei W; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Xu J; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Ya Y; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zhang J; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Hou X; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Zhai Q; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zha Z; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zhuo Y; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zhou Y; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Yuan H; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Liang Y; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Han Z; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zhong W; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China., Zhu L; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Chen Y; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Jazyk: angličtina
Zdroj: Asia-Pacific journal of clinical oncology [Asia Pac J Clin Oncol] 2022 Apr; Vol. 18 (2), pp. e46-e55. Date of Electronic Publication: 2021 Feb 19.
DOI: 10.1111/ajco.13551
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.
(© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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