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1 May 2007 Purvalanol A Enhances Cell Killing by Inhibiting Up-Regulation of CDC2 Kinase Activity in Tumor Cells Irradiated with High Doses of X Rays
Daisuke Iizuka, Osamu Inanami, Ikuo Kashiwakura, Mikinori Kuwabara
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Abstract

Iizuka, D., Inanami, O., Kashiwakura, I. and Kuwabara, M. Purvalanol A Enhances Cell Killing by Inhibiting Up-Regulation of CDC2 Kinase Activity in Tumor Cells Irradiated with High Doses of X Rays. Radiat. Res. 167, 563–571 (2007).

To clarify the relationship between CDC2 kinase activity and radiation-induced apoptosis, we examined whether the cyclin-dependent kinase (CDK) inhibitor purvalanol A enhanced radiation-induced apoptosis in gastric tumor cells. MKN45 cells exposed to 20 Gy of X rays increased the CDC2 kinase activity and the expression of regulatory proteins (phospho-CDC2 and cyclin B1) of the G2/M phase, followed by activation of the G2/M checkpoint, whereas the treatment of X-irradiated MKN45 cells with 20 μM purvalanol A suppressed the increase in the CDC2 kinase activity and expression of the G2/M-phase regulatory proteins and reduced the fraction of the cells in the G2/M phase in the cell cycle. Furthermore, this treatment resulted in not only a significant increase in radiation-induced apoptosis but also the loss of clonogenicity in both MKN45 (p53-wild) and MKN28 (p53-mutated) cells. The expression of anti-apoptosis proteins, inhibitor of apoptosis protein (IAP) family members (survivin and XIAP) and BCL2 family members (Bcl-XL and Bcl-2), in purvalanol A-treated cells with and without X rays was significantly lower than for cells exposed to X rays alone. These results suggest that the inhibition of radiation-induced CDC2 kinase activity by purvalanol A induces apoptosis through the enhancement of active fragments of caspase 3.

Daisuke Iizuka, Osamu Inanami, Ikuo Kashiwakura, and Mikinori Kuwabara "Purvalanol A Enhances Cell Killing by Inhibiting Up-Regulation of CDC2 Kinase Activity in Tumor Cells Irradiated with High Doses of X Rays," Radiation Research 167(5), 563-571, (1 May 2007). https://doi.org/10.1667/RR0622.1
Received: 14 March 2006; Accepted: 1 November 2006; Published: 1 May 2007
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