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Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines.
J Orthop Res. 2006 Jun; 24(6):1153-62.JO

Abstract

Molecular mechanisms underlying chemotherapeutic agent-induced apoptosis in sarcoma cells are not well known. Induction of apoptosis is regulated by several components including mitogen-activated protein kinases (MAPKs) comprising ERK, p38MAPKs, and c-Jun N-terminal kinase (JNK). In the present study, we examined whether activation of JNK is induced by the chemotherapeutic agents cis-diaminedichloroplatinum (cisplatin, CDDP) or doxorubicin (DXR), and whether the ectopic expression of constitutively active (MKK7-JNK1) or dominant-negative form of JNK (dnJNK) influenced apoptosis in response to the CDDP or DXR in sarcoma cell lines MG-63 and SaOS-2. The CDDP or DXR induced JNK activation in the both cell lines, as assessed by Western blotting using phosphospecific antibodies. A transient expression of the activated form of JNK sensitized the MG-63 and SaOS-2 cells to the drug-induced apoptosis, while dnJNK1 reduced the proportion of apoptotic cell death. Apoptosis was determined by flow cytometry using annexin-V Cy5. Collectively, our results indicate that JNK activation is involved in apoptotic cell death in sarcoma cell lines following stimulation with CDDP or DXR.

Authors+Show Affiliations

Department of Immunology, Tokyo Medical University, Tokyo, 160-8402 Japan.No 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

16705697

Citation

Koyama, Takaaki, et al. "Apoptosis Induced By Chemotherapeutic Agents Involves c-Jun N-terminal Kinase Activation in Sarcoma Cell Lines." Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, vol. 24, no. 6, 2006, pp. 1153-62.
Koyama T, Mikami T, Koyama T, et al. Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines. J Orthop Res. 2006;24(6):1153-62.
Koyama, T., Mikami, T., Koyama, T., Imakiire, A., Yamamoto, K., Toyota, H., & Mizuguchi, J. (2006). Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines. Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 24(6), 1153-62.
Koyama T, et al. Apoptosis Induced By Chemotherapeutic Agents Involves c-Jun N-terminal Kinase Activation in Sarcoma Cell Lines. J Orthop Res. 2006;24(6):1153-62. PubMed PMID: 16705697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines. AU - Koyama,Takaaki, AU - Mikami,Takashi, AU - Koyama,Takashi, AU - Imakiire,Atsuhiro, AU - Yamamoto,Kengo, AU - Toyota,Hiroko, AU - Mizuguchi,Junichiro, PY - 2006/5/18/pubmed PY - 2006/6/30/medline PY - 2006/5/18/entrez SP - 1153 EP - 62 JF - Journal of orthopaedic research : official publication of the Orthopaedic Research Society JO - J Orthop Res VL - 24 IS - 6 N2 - Molecular mechanisms underlying chemotherapeutic agent-induced apoptosis in sarcoma cells are not well known. Induction of apoptosis is regulated by several components including mitogen-activated protein kinases (MAPKs) comprising ERK, p38MAPKs, and c-Jun N-terminal kinase (JNK). In the present study, we examined whether activation of JNK is induced by the chemotherapeutic agents cis-diaminedichloroplatinum (cisplatin, CDDP) or doxorubicin (DXR), and whether the ectopic expression of constitutively active (MKK7-JNK1) or dominant-negative form of JNK (dnJNK) influenced apoptosis in response to the CDDP or DXR in sarcoma cell lines MG-63 and SaOS-2. The CDDP or DXR induced JNK activation in the both cell lines, as assessed by Western blotting using phosphospecific antibodies. A transient expression of the activated form of JNK sensitized the MG-63 and SaOS-2 cells to the drug-induced apoptosis, while dnJNK1 reduced the proportion of apoptotic cell death. Apoptosis was determined by flow cytometry using annexin-V Cy5. Collectively, our results indicate that JNK activation is involved in apoptotic cell death in sarcoma cell lines following stimulation with CDDP or DXR. SN - 0736-0266 UR - https://www.unboundmedicine.com/medline/citation/16705697/Apoptosis_induced_by_chemotherapeutic_agents_involves_c_Jun_N_terminal_kinase_activation_in_sarcoma_cell_lines_ L2 - https://doi.org/10.1002/jor.20176 DB - PRIME DP - Unbound Medicine ER -