Inhibition of X-ray and Doxorubicin-induced Apoptosis by Butyrolactone I, a CDK-specific Inhibitor, in Human Tumor Cells

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概要

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• Cell-cycle progression is coordinately regulated by cyclin-dependent kinases (CDKs). The inhibition of CDKs by p21^<Waf1/Cip1/Sdi1> prevents the apoptosis of cells treated with DNA-damaging agents. In this study, we found that butyrolactone I, a specific inhibitor of CDC2 family kinases, blocks the X-ray- or doxorubicin- induced apoptosis of DLD1 (p21+/+) human colorectal carcinoma cells in a dose-dependent manner. We also found that butyrolactone I inhibits the CDK2 activity and enhances cell survival after an X-ray irradiation or doxorubicin treatment in both DLD1 (p21-/-) and DLD1 (p21+/+) cells. These findings suggest that butyrolactone I prevents apoptosis by the direct inhibition of CDK and also, possibly, by CDKinhibition through p53-independent p21-induction. Our findings indicate that CDK activity is required for DNA-damaging agent-induced apoptosis.

• 日本放射線影響学会の論文

著者

• Yagi Takashi

  Department of Cardiology, Keio University School

• Yagi Takashi

  京都大学 医研究 放射線遺伝

• Yagi Takashi

  Department Of Radiation Genetics Graduate School Of Medicine Kyoto University:division Of Radiobiolo

• TAKEBE Hiraku

  Department of Radiation Genetics, Faculty of Medicine, Kyoto University

• Takebe Hiraku

  Department Of Radiation Genetics Faculty Of Medicine Kyoto University

• Takebe Hiraku

  Department Of Radiation Genetics Graduate School Of Medicine Kyoto University: Research Reactor Inst

• Takebe Hiraku

  京都大学医学部放射能基礎医学教室

• Takebe Hiraku

  Dept. Radiat. Gen. Fac. Med. Kyoto Univ.

• Lu Yanjun

  Department Of Radiation Genetics Graduate School Of Medicine Kyoto University:cancer Research Center

• Yagi Takashi

  大阪府立大学先端科学研究所

• YAGI TAKASHI

  Department of Bio and Geo Sciences, Graduate School of Science, Osaka City University

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