A Novel Hydroxymethoxynaphthochalcone Induces Apoptosis Through the p53-dependent Caspase-mediated Pathway in HCT116 Human Colon Cancer Cells

摘要

Flavonoids have always been studied in the context of therapies of human diseases. Among them, chalcone, an open-chain flavonoid, has been used as a key precursor for synthetic lead compounds due to its diverse innate biological activity. Additionally, benzoflavone is known to induce xenobiotic-metabolizing enzyme activity, as well as have potent chemopreventive activity. Therefore, the combined structure of these two compounds should be useful for the discovery of new and/or increased biological activity. In this study, a chalcone derivative, 2'-hydroxy-2,4,6-trimethoxy-5',6'-naphthochalcone (HMNC-74), was synthesized, and its anticancer activity was tested in the HCT116 human colon cancer cell line. An in silico docking study showed that HMNC-74 binds to tubulin. HMNC-74 exhibited the inhibition of clonogenicity of HCT116 cells and cell cycle arrest at the G2/M phase, followed by induction of apoptosis through, at least in part, p53-dependent caspase-7 activation. The results of this study show that HMNC-74 may be an effective chemotherapeutic agent