Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines. |
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Authors: | Takaaki Koyama Takashi Mikami Takashi Koyama Atsuhiro Imakiire Kengo Yamamoto Hiroko Toyota Junichiro Mizuguchi |
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Institution: | Department of Immunology, Tokyo Medical University, Tokyo, 160-8402 Japan. |
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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. |
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Keywords: | sarcoma cells apoptosis c‐Jun N‐terminal kinase (JNK) cis‐diaminedichloroplatinum (CDDP) doxorubicin (DXR) |
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