In the present study, it was investigated that the effects of mitogen-activated protein kinases (MAPK) signal pathway on the apoptosis induction of Hep3B human hepatocarcinoma cells by a synthetic methyl jasmonate derivative (methyl 5-chloro-4,5-didehydrojasmonate, J-7). We found that treatment of Hep3B cells with J-7 markedly increased phospholylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK), and pretreatment an ERK-specific inhibitor, PD98059, and a JNK-specific inhibitor, SP600125, showed increased anti-proliferative action and apoptosis by J-7. The synergistic increased apoptotic events in Hep3B cells caused by blocking the ERK and JNK pathways were associated an up-regulation of death receptor 5 (DR5) and a decrease of Bid, X-linked inhibitor of apoptosis protein (XIAP) and cIAP-1 expression. Additionally, our results also indicated that the increased apoptosis by co-administration of PD98059 and SP600125 with J-7 in Hep3B cells was connected with the down-regulation of pro-caspases (-3, -8 and -9). Taken together, these findings suggest that apoptotic cell death by J-7 in Hep3B cells are associated with the activation of the ERK and JNK pathways. (Cancer Prev Res 16, 126-133, 2011)

Keywords: J-7, Hep3B, Apoptosis, ERK, JNK