PMID: 11329882May 2, 2001Paper

Inhibition of X-ray and doxorubicin-induced apoptosis by butyrolactone I, a CDK-specific inhibitor, in human tumor cells

Journal of Radiation Research
Y LuT Yagi

Abstract

Cell-cycle progression is coordinately regulated by cyclin-dependent kinases (CDKs). The inhibition of CDKs by p21Waf1/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 CDK-inhibition through p53-independent p21-induction. Our findings indicate that CDK activity is required for DNA-damaging agent-induced apoptosis.

References

Aug 1, 1995·Experimental Cell Research·C Y Gao, P S Zelenka
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·A T HoangC V Dang
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·W MeikrantzR Schlegel
Apr 26, 1996·The Journal of Biological Chemistry·W Meikrantz, R Schlegel
Sep 28, 1999·Oncogene·L Delavaine, N B La Thangue

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