Disulfiram‐copper activates chloride currents and induces apoptosis with tyrosine kinase in prostate cancer cells
| Autor: | Jingkui Xu, Wei Lei, Yiyao Ya, Jinxiang Zhang, Xiuying Hou, Hong Yuan, Zeyu Zha, Yehui Chen, Zhao-Dong Han, Linyan Zhu, You Zhou, Qiliang Zhai, Yuxiang Liang, Weide Zhong, Yangjia Zhuo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.drug_class Genistein Apoptosis Tyrosine-kinase inhibitor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chlorides Western blot Chloride Channels Cell Line Tumor Disulfiram LNCaP Humans Medicine 030212 general & internal medicine PTK2B medicine.diagnostic_test business.industry Prostatic Neoplasms General Medicine Protein-Tyrosine Kinases Molecular biology Molecular Docking Simulation Oncology chemistry 030220 oncology & carcinogenesis Chloride channel business Tyrosine kinase Copper |
| Zdroj: | Asia-Pacific Journal of Clinical Oncology. 18 |
| ISSN: | 1743-7563 1743-7555 |
| DOI: | 10.1111/ajco.13551 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text