Molecular Mechanism Study Of 3,5-Dimethyl-7H-Furo[3,2-g]Chromen-7-One Induced Apoptosis In Human Liver Cancer

3,5-Dimethyl-7H-Furo[3,2-g]Chromen-7-One (DMFC) is a coumarin derivative with anti-cancer activity against human liver cancer HepG2. However, the molecular mechanism is still unclear. In this study, we aimed at elucidating the molecular mechanisms underlying DMFC function and determining the efficacy of DMFC in suppression of drug-resistant human liver cancer. We observed that DMFC suppresses tumor cell growth through inducing apoptosis, and DMFC is effective in induction of apoptosis in multidrug-resistant human liver cancer cells both in vitro and in vitro. Our further research observed that DMFC downgrades Bcl-2 at the post-transcriptional level and upgrades Bim at the transcriptional level. Furthermore, DMFC upgrades Bim to disturb the interaction between Bcl-2 and Bax, Mcl-1 and Bak, resulting in the displacement of Bax from Bcl-2 and Bak from Mcl-1. Combination of the activation of Bax and Bak, DMFC induces the mitochondrial outer membrane permeabilization and a series of effects such as cytochrome c release. Consistent with its in vitro apoptosis induction activity, DMFC exhibited potent activity against multidrug-resistant liver cancer xenograft growth in vivo.In conclusion, DMFC induces Bim upregulation to cooperatively trigger Bax and Bak activation to suppress multidrug-resistant human liver cancer growth in vivo, and thus holds great promise for development as an effective small molecule anti-cancer agent in human liver cancer therapy to overcome drug resistance.