| Project/Area Number |
20790940
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Kansai Medical University |
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Principal Investigator |
UEHARA Norihisa Kansai Medical University, 医学部, 講師 (30368211)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | HDAC inhibitor / G2 / M arrest / Skp2 / Cks1 / apoptosis / p38MAPK / breast cance / Apotosis / p38 MAPK / breast cancer / Breast cancer / Histone deacetylase / Growth arrest / Apoptosis |
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| Research Abstract |
Vorinostat is an inhibitor of histone deacetylases that effectively suppresses proliferation of various cancer cells by inducing cell cycle arrest and/or apoptosis. However, signaling events leading to apoptosis in response to vorinostat is not fully understood. In the present study, we found that vorinostat induced G2/M cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Vorinostat-treated MDA-MB-231 cells exhibited the accumulation of p27 protein, which inversely correlated with the Skp2 and CKs1 expression, the components of SCF^<Skp2-Cks1> ubiquitin ligase complex. Our results constitute novel evidence that the elevation of p21 and p27 level by vorinostat may be in part due to the down-regulation of Skp2 and Cks1. Furthermore, we found that vorinostat triggered the intrinsic apoptosis pathway, which was associated with the accumulation of acetylated histone H3. Our data provide strong evidence that the activation of p38 MAPK is a crucial event in the apoptotic response to vorinostat in MDA-MB-231 cells. These findings could provide useful insights into more effective cancer therapies.
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