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

• Published in: Applied biological chemistry 2014-08, Vol.57 (4), p.413-418
• Main Authors: Shin, Soon Young, Yong, Yeonjoong, Lee, Jongmin, Ahn, Seunghyun, Jung, Kang-Yeoun, Koh, Dongsoo, Lee, Young Han, Lim, Yoongho
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antitumor activity; Apoptosis; Applied Microbiology; Biological activity; Biological Techniques; Bioorganic Chemistry; Caspase-7; Cell cycle; Chemistry; Chemistry and Materials Science; Colon; Colon cancer; Colorectal cancer; Enzymatic activity; Enzyme activity; Flavonoids; Lead compounds; p53 Protein; Tubulin
• ISSN: 1738-2203; 2468-0834; 2234-344X; 2468-0842
• DOI: 10.1007/s13765-014-4043-y

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.