2004年3月
A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: Involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation
CANCER RESEARCH
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- 巻
- 64
- 号
- 6
- 開始ページ
- 2134
- 終了ページ
- 2142
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1158/0008-5472.CAN-03-2296
- 出版者・発行元
- AMER ASSOC CANCER RESEARCH
In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis and the involvement of mitogen-activated protein kinases (MAPKs). The exposure of Jurkat human T-cell leukemia cells to BITC resulted in the inhibition of the G(2)-M progression that coincided with the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G(2)-M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We also confirmed that BITC activated c-Jun N-terminal kinase (JNK) and p38 MAPK, but not extracellular signal-regulated kinase, at the concentration required for apoptosis induction. An experiment using a JNK-specific inhibitor SP600125 or a p38 MAPK inhibitor SB202190 indicated that BITC-induced apoptosis might be regulated by the activation of these two kinases. Conversely, BITC is likely to confine the Jurkat cells in the G(2)-M phase mainly through the p38 MAPK pathway because only the p38 MAPK inhibitor significantly attenuated the accumulation of inactive phosphorylated Cdc2 protein and the G(2)-M- arrested cell numbers. We reported here for the first time that the antiapoptotic Bcl-2 protein was phosphorylated by the BITC treatment without significant alteration of the Bcl-2 total protein amount. This was abrogated by a JNK specific inhibitor SP600125 at the concentration required for specific inhibition of the c-Jun phosphorylation. Moreover, the spontaneous phosphorylation of antiapoptotic Bcl-2 in the G(2)-M synchronized cells was enhanced synergistically by the BITC treatment. Involvement of the MAPK activation in the Bcl-2 phosphorylation and apoptosis induction also was observed in HL-60 and HeLa cells. Thus, we identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC.
- リンク情報
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- DOI
- https://doi.org/10.1158/0008-5472.CAN-03-2296
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/15026354
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000220249100036&DestApp=WOS_CPL
- URL
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=1542615077&origin=inward
- ID情報
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- DOI : 10.1158/0008-5472.CAN-03-2296
- ISSN : 0008-5472
- PubMed ID : 15026354
- SCOPUS ID : 1542615077
- Web of Science ID : WOS:000220249100036