Reference - Detail
| RRC ID | 1385 |
|---|---|
| Author | Miyoshi N, Uchida K, Osawa T, Nakamura Y. |
| Title | A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation. |
| Journal | Cancer Res |
| Abstract |
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. |
| Volume | 64(6) |
| Pages | 2134-42 |
| Published | 2004-3-15 |
| DOI | 10.1158/0008-5472.can-03-2296 |
| PMID | 15026354 |
| MeSH | Apoptosis / drug effects* CDC2 Protein Kinase / metabolism Cell Cycle / drug effects* Enzyme Inhibitors / pharmacology HL-60 Cells HeLa Cells Humans Isothiocyanates / pharmacology* JNK Mitogen-Activated Protein Kinases* Jurkat Cells MAP Kinase Kinase 4 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases / metabolism Mitogen-Activated Protein Kinases / metabolism* Phosphorylation / drug effects Proto-Oncogene Proteins c-bcl-2 / metabolism* Signal Transduction p38 Mitogen-Activated Protein Kinases |
| IF | 9.727 |
| Times Cited | 115 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Jurkat(RCB0806) |