In Vivo Metabolites of Panaxadiol Inhibit HepG-2 Cell Proliferation by Inducing G1 Arrest and ROS-Mediated Apoptosis

In this study, 10 metabolites were obtained by collecting and extracting fecal samples after oral administration of panaxadiol (PD). Of these 10 metabolites, M7 (3β,21β,22α-hydroxy-24-norolean-12-ene), M8 (21β,22α-hydroxy-24-norolean-12-ene-3-one), M9 (3β,30α-hydroxy-24-norolean-22,30-epoxy-12-ene), and M10 (3β,21β-hydroxy-24-norolean-12-ene) were new compounds. MTT screening of the isolated compounds revealed that the inhibitions of cancer cells by M2, M4, M7, M8, and M10 were significantly stronger than that by the mother drug M0, with the activity of M2 being the most significant. Further, we investigated the anticancer mechanism of M2. The results showed that M2 significantly increased the level of ROS in cells; regulated the expressions of Bax, Bcl-2, and Cyt-C through the mitochondrial pathway; triggered the caspase cascade; and induced apoptosis. M2 could also induce G1 phase arrest and significantly regulate cell cycle-related proteins. In conclusion, the experimental results provide data for further study on the metabolic mechanism of PD in vivo and the potential of developing new anti-cancer drugs.