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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.
Anticancer Res. 2006 Mar-Apr; 26(2A):1153-60.AR

Abstract

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.

Authors+Show Affiliations

Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16619517

Citation

Mikami, Takashi, et al. "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." Anticancer Research, vol. 26, no. 2A, 2006, pp. 1153-60.
Mikami T, Koyama T, Koyama T, et al. 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. Anticancer Res. 2006;26(2A):1153-60.
Mikami, T., Koyama, T., Koyama, T., Imakiire, A., Yamamoto, K., Furuhata, M., Toyota, H., & Mizuguchi, J. (2006). 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. Anticancer Research, 26(2A), 1153-60.
Mikami T, et al. 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. Anticancer Res. 2006 Mar-Apr;26(2A):1153-60. PubMed PMID: 16619517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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. AU - Mikami,Takashi, AU - Koyama,Takaaki, AU - Koyama,Takashi, AU - Imakiire,Atsuhiro, AU - Yamamoto,Kengo, AU - Furuhata,Masae, AU - Toyota,Hiroko, AU - Mizuguchi,Junichiro, PY - 2006/4/20/pubmed PY - 2006/5/12/medline PY - 2006/4/20/entrez SP - 1153 EP - 60 JF - Anticancer research JO - Anticancer Res VL - 26 IS - 2A N2 - 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. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/16619517/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_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=16619517 DB - PRIME DP - Unbound Medicine ER -