A novel hydroxymethoxynaphthochalcone induces apoptosis through the p53-dependent caspase-mediated pathway in HCT116 human colon cancer cells

Abstract

Flavonoids have always been studied in the context of therapies of human diseases. Among them, chalcone, an openchain 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.