Inhibitors of phosphatidylinositol 3-kinase activity prevent cell cycle progression and induce apoptosis at the M/G1 transition in CHO cells |
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Authors: | A. van Opstal J. Boonstra |
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Affiliation: | (1) Cellular Architecture & Dynamics, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands |
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Abstract: | Phosphatidylinositol 3-kinase (PI3-kinase) activity has been implicated in regulating cell cycle progression at distinct points in the cell cycle by preventing cell cycle arrest or apoptosis. In this study, the role of PI3-kinase activity during the entire G1 phase of the ongoing cell cycle was studied in Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off. We show that inhibition of PI3-kinase activity during and 2 h after mitosis inhibited cell cycle progression into S phase. In the presence of the PI3-kinase inhibitor wortmannin or LY294002, cells were arrested during early G1 phase, leading to the expression of the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PI3-kinase activity is required for progression through the M/G1 phase. In the absence of PI3-kinase activity, cells are induced for apoptosis in this particular phase of the cell cycle. Received 7 September 2005; received after revision 26 October 2005; accepted 11 November 2005 |
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Keywords: | Phosphatidylinositol 3-kinase cell cycle progression apoptosis G1 phase actin |
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