Compound for Cancer Treatment

The therapeutic toxicity and resistance to currently available treatment options are major clinical challenges for the management of lung cancer. As a novel strategy, researchers synthesized analogues of a known flavonol, fisetin, which has shown anti-tumorigenic potential against cancer in cell culture with no adverse effects in animal models. Researchers studied the synthetic analogues of fisetin for their anti-cancer potential against lung cancer cells and evaluated its toxicity and efficacy in a xenograft mouse model for cancer. Brominated fisetin analogues were screened for their effects on the viability of A549 and H1299 lung cancer cells, and three analogues (3a, 3b, 3c), showed much improved cytotoxicity compared to fisetin. These analogues were more effective in restricting lung cancer cell proliferation, inducing G2M phase cell cycle arrest and apoptosis. The fisetin analogues also downregulated EGFR/ERK1/2/STAT3 pathways. Fisetin analogue-induced apoptosis was accompanied with a higher level of Bax to Bcl-2 expression ratio. Based on the in vitro studies, the most effective fisetin analogue 3b was evaluated for in vivo toxicity, wherein it did not show any hepatotoxicity and adverse health effects in mice. Further, fisetin analogue 3b showed greater antitumor efficacy (P<0.001) as compared to the parent compound fisetin in a human lung cancer cell xenograft study in athymic mice. Together our data suggest that the novel fisetin analogue 3b is more effective in restricting lung cancer cells growth, both in vitro as well as in vivo, without any apparent toxicity, supporting its use and thus it may be development as a novel anti-lung cancer agent.