Chemo-enzymatic cascade processes are invaluable due to their ability to rapidly construct high-value products from available feedstock chemicals in a one-pot relay manner. In an article, author is Lei, Wei, once mentioned the application of 85-54-1, Name is 2-(4-Chloro-3-nitrobenzoyl)benzoic acid, molecular formula is C14H8ClNO5, molecular weight is 305.67, MDL number is MFCD00007082, category is chlorides-buliding-blocks. Now introduce a scientific discovery about this category, Computed Properties of C14H8ClNO5.
Disulfiram-copper activates chloride currents and induces apoptosis with tyrosine kinase in prostate cancer cells
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 2 beta (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.
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