A methyl jasmonate derivative, J-7, induces apoptosis in human hepatocarcinoma Hep3B cells in vitro.
The pro-apoptotic activity of J-7, a synthetic methyl jasmonate derivative, on the Hep3B human hepatocarcinoma cell line was investigated. Treatment of Hep3B cells with J-7 resulted in growth inhibition and the induction of apoptosis as measured by trypan blue-excluding cells, MTT assay, nuclear staining, DNA fragmentation, and flow cytometry analysis. The increased apoptotic events in Hep3B cells caused by J-7 were associated with the alteration in the ratio of Bax/Bcl-2 protein expression. J-7 treatment induced the expression of death receptor-related proteins such as death receptor 5, which triggered the activation of caspase-8 and the down-regulation of the whole Bid expression. In addition, the apoptosis induction by J-7 was correlated with the activation of caspase-9 and caspase-3, down-regulation IAP family proteins such as XIAP and cIAP-1, and concomitant degradation of poly (ADP-ribose) polymerase. However, the cytotoxic and apoptotic effects induced by J-7 were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the process. Furthermore, blocking the extracellular signal-regulated protein kinase and c-Jun N-terminal kinase pathways showed increased apoptosis and the activation of caspases in J-7-induced apoptosis. The results indicated that J-7 induces the apoptosis of Hep3B cells through a signaling cascade of death-receptor-mediated extrinsic as well as mitochondria-mediated intrinsic caspase pathways, which are associated with the activation of the mitogen-activated protein kinases signal pathway.
Park
Cheol
C
Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-714, South Korea.
Jin
Cheng-Yun
CY
Kim
Gi-Young
GY
Cheong
JaeHun
J
Jung
Jee H
JH
Yoo
Young Hyun
YH
Choi
Yung Hyun
YH
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D053218:Receptors, Death Domain / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D053218:Receptors, Death Domain; C555027:methyl 5-chloro-4,5-didehydrojasmonate; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases