Enhancing the chemosensitivity of HepG2 cells towards cisplatin by organoselenium pseudopeptides

Despite all recent advances in the treatment of hepatocellular carcinoma (HCC), chemotherapy resistance still represents a major challenge in its successful clinical management. Chemo-sensitization offers an attractive strategy to counter drug resistance. Herein we report the identification of novel organoselenium-based pseudopeptides as promising highly effective chemo-sensitizers in treating HCC with cisplatin. A series of functionalized pseudopeptide- (5?9 and 17?19), peptidomimetic- (10?12 and 20?23), and tetrazole-based (13?16 and 24?27) organoselenium compounds were synthesized via isonitrile-based multicomponent reactions from two novel selenium-containing isocyanides. All compounds were evaluated for their cytotoxicity against HepG2 and the non-cytotoxic doses were used to restor the sensitivity of the cells to cisplatin. New organoselenium compounds (7, 9, 15, or 23) led to an effective chemo-sensitization of HepG2 cells towards cisplatin (up-to 27-fold). Cell cycle studies indicate that the most potent peptidomimetic diselenide 23 arrested cells at the S phase and induced apoptosis via ROS modulation.

Automated summary

Recent research has uncovered a novel organoselenium-based pseudopeptide that shows promising efficacy in treating hepatocellular carcinoma, making cells more sensitive to cisplatin and inducing apoptosis by modulating ROS levels.