(S)-3-(3-Fluoro-4-Methoxybenzyl)-5,6,7-Trimethoxychroman4-One Suppresses the Proliferation of Huh7 Cells by Up-regulating P21 and Inducing G2/M Phase Arrest

Background/Aim: Hepatocellular carcinoma (HCC) is a prevalent type of cancer worldwide. Although sorafenib is the only chemotherapy agent used for HCC, there is a need to discover a more potent anticancer agent with reduced side- effects. The compound, (S)-3-( 3-fluoro-4-methoxybenzyl)-5,6,7-trimethoxychroman-4-one ( FMTC), was designed to inhibit tubulin assembly but its specific mechanisms of action have not been previously investigated. Herein, we investigated the regulation mechanisms by which FMTC affects the proliferation of the HCC cell line, Huh7. Materials and Methods: The effects of FMTC on cell viability and growth were analyzed in the HCC cell line, Huh7. Cell cycle and apoptosis regulated by FMTC were analyzed using flow cytometry. To verify the regulation of mRNA and protein expression of cell proliferation- related factors by FMTC in Huh7 cells, RT-qPCR and western blot analyses were employed. Results: FMTC suppressed cell division dose-dependently by triggering cell cycle arrest at the G(2)/ M phase via p21 up-regulation. The increased phosphorylation of histone H3 on Ser-10 and the condensation of chromatin in FMTC-treated cells indicated mitotic arrest. Prolonged FMTC-induced cell cycle arrest triggered apoptosis. Conclusion: FMTC inhibits the proliferation of human liver cancer cells by up-regulating p21, thereby inducing cell cycle arrest at the G(2)/M phase. These findings highlight FMTC as a novel agent for HCC treatment. Liver cancer