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6-[(1-naphthylmethyl)sulfanyl]-9H-purine (NMMP) is a derivative of 6-Mercaptopurine.We have demonstrated that NMMP reduced the viability of HepG2 cells but not normal hepatocytes in a timeand dose-dependent manner.NMMP could arrest cell cycle in G2/M phase via the reduction of CDK4 and cyclin D1/B1 levels.Using western blot analysis, we showed that NMMP-induced cell cycle arrest is followed by apoptosis.We determine further that NMMP-induced apoptosis is accomplished by the rmitochondria-dependent activation of the caspase cascade.Luciferase reporter assays reveal that NMMP suppresses the ERK1/2 MAPK pathway and activate p53 pathway.Overall, these data suggest NMMP has antitumor activity through inhibition of proliferation and induction of apoptosis, implicating its potential therapeutic value for the treatment of Hepatocellular cancer.