Ipriflavone, a synthetic
isoflavone that inhibits osteoclastic
bone resorption, has been used clinically for the treatment of
osteoporosis. However, the anticancer activity of
Ipriflavone and its molecular mechanisms in the context of
esophageal squamous cell carcinoma (ESCC) have not been investigated. In this study, we report that
Ipriflavone is a novel
mammalian target of rapamycin (mTOR) inhibitor that suppresses cell proliferation and induces cell apoptosis in ESCC cells.
Ipriflavone inhibited anchorage-dependent and -independent growth of ESCC cells.
Ipriflavone induced G1 phase cell cycle arrest and intrinsic cell apoptosis by activating
caspase 3 and increasing the expression of
cytochrome c. Based on the results of in vitro screening and cell-based assays,
Ipriflavone inhibited mTOR signaling pathway through directly targeting mTOR. Knockdown of mTOR strongly inhibited the growth of ESCC cells, and the cell growth inhibitory effect exerted by
Ipriflavone was found to be dependent upon mTOR signaling pathway. Remarkably,
Ipriflavone strongly inhibited ESCC patient-derived xenograft
tumor growth in an in vivo mouse model. Our findings suggest that
Ipriflavone is an mTOR inhibitor that could be potentially useful for treating ESCC.