RT Journal Article
SR Electronic
T1 c-Jun N-terminal Kinase Activation is Required for Apoptotic Cell Death Induced by TNF-related Apoptosis-inducing Ligand plus DNA-damaging Agents in Sarcoma Cell Lines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1153
OP 1160
VO 26
IS 2A
A1 TAKASHI MIKAMI
A1 TAKAAKI KOYAMA
A1 TAKASHI KOYAMA
A1 ATSUHIRO IMAKIIRE
A1 KENGO YAMAMOTO
A1 MASAE FURUHATA
A1 HIROKO TOYOTA
A1 JUNICHIRO MIZUGUCHI
YR 2006
UL http://ar.iiarjournals.org/content/26/2A/1153.abstract
AB Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in combination with a chemotherapeutic agent, cis-diammine dichloroplatinum (CDDP) or doxorubicin (DXR), has recently been demonstrated to result in enhanced apoptotic cell death in the sarcoma cell lines MG-63 and SaOS-2. DNA-damaging agents, such as CDDP induced sustained activation of c-Jun N-terminal kinase (JNK), probably leading to apoptosis. In the present study, whether JNK activation is involved in apoptotic cell death induced by combined treatment with CDDP/DXR and TRAIL was addressed. Results: MG-63 or SaOS-2 cells overexpressing the dominant-negative (dn) form of JNK (dnJNK1) were established by transfection with dnJNK1 cDNA. Following stimulation with the chemotherapeutic agent CDDP or TRAIL, both MG-63 and SaOS-2 cells demonstrated enhanced cell death compared with stimulation by either agent alone, as assayed for apoptosis using annexin V staining or mitochondrial membrane potential using DiOC6 staining. Interestingly, partial inhibition of the cell death induced by the combined treatment with CDDP/DXR and TRAIL was found in MG-63 or SaOS-2 cells overexpressing dnJNK1, suggesting that JNK activation is required for the combined treatment. Moreover, induction of caspase-8 activation by TRAIL or TRAIL plus CDDP/DXR was substantially prevented by dnJNK. Conclusion: Efficient cell death induced by combined treatment with the chemotherapeutic agents CDDP/DXR and TRAIL is involved in JNK activation in the sarcoma cell lines MG-63 and SaOS-2. These results would be useful for treatment modalities of patients with sarcoma. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved