Novel hybrids of podophyllotoxin and formononetin inhibit the growth, migration and invasion of lung cancer cells

In this study, three hybrids of podophyllotoxin and formononetin were synthesized and evaluated for anticancer efficacy. Some of the derivatives exhibited potent cytotoxicity against a panel of human and mouse cancer cell lines, with IC50 values in the low micromolar to submicromolar range. Evaluation against A549 lung tumor cell line identified that the IC50 value of compound 10a was 0.753 mu M, indicating that 10a was 2.568-fold more efficacious than parent podophyllotoxin. Mechanistic studies revealed that 10a induced A549 cell apoptosis mainly via caspase pathway, as well as disrupted the microtubule organization by occupying the colchicine binding site of the tubulin. Moreover, wound healing assay and transwell invasion assay indicated that 10a displayed potent inhibitory effects on invasion and migration in A549 cancer cells. In additiona, a decrease in vimentin immunostaining was also observed in A549 cells after treatment with 10a. Overall, hybrid 10a might be a promising candidate for the potential treatment of human lung carcinoma.