Gossypol enhances ponatinib's cytotoxicity against human hepatocellular carcinoma cells by involving cell cycle arrest, p-AKT/LC3II/p62, and Bcl2/caspase-3 pathways.

Despite significant breakthroughs in frontline cancer research and chemotherapy for hepatocellular carcinoma (HCC), many of the suggested drugs have high toxic side effects and resistance, limiting their clinical utility. Exploring potential therapeutic targets or novel combinations with fewer side effects is therefore crucial in combating this dreadful disease. The current study aims to use a novel combination of ponatinib and gossypol against the HepG2 cell line.

The ponatinib/gossypol novel combination provides enhanced anticancer activity against murine solid Ehrlich carcinoma via triggering apoptosis and inhibiting proliferation/angiogenesis.

The search for new antitumor agents or combinations that are more effective and, hopefully, provide fewer health hazards is ongoing. Therefore, this study investigated the efficacy of a novel combination of ponatinib, a multi-targeted tyrosine kinase inhibitor, and the natural phytochemical gossypol against murine solid Ehrlich carcinoma. Six groups of ten mice each received vehicle (I), ponatinib in doses of 10 and 15 mg/kg (II, III) respectively, gossypol in a dose of 4 mg/kg (IV), and ponatinib (10 or 15 mg/kg) in combination with gossypol (4 mg/kg; V, VI).