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It has been shown that flavonoids have anti-tumor activity. In this study, LZ-205, a newly synthesized flavonoid, was found to be effective in inducing apoptosis in human lung cancer cells in vivo and in vitro. Mechanistically, LZ-205 triggers reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress and unfolded protein response, which could be reversed by silencing CHOP, a mediator of the ER stress-associated apoptosis. In addition, LZ-205-induced apoptosis is accompanied by the activation of both the mitochondrial apoptotic and extrinsic pathways, followed by decreased mitochondrial membrane potential (ΔΨm) and the alteration of the expression of mitochondria-related pro- and anti-apoptotic proteins. LZ-205 exhibits a potential antitumor effect in BALB/c nude mice bearing H460 tumor with low systemic toxicity. In summary, both the ROS-mediated ER stress pathway and the exogenous apoptotic pathway are involved in LZ-205-induced apoptosis in vitro and in vivo. Our data show a therapeutic potential of LZ-205 for the treatment of lung cancer.

Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in human lung cancer cells by the new synthetic flavonoid, LZ-205