Inhibitors of phosphatidylinositol 3-kinase activity prevent cell cycle progression and induce apoptosis at the M/G1 transition in CHO cells.
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.
van Opstal
A
A
Cellular Architecture & Dynamics, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Boonstra
J
J
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D016193:G1 Phase / Q000187:drug effects*; D008938:Mitosis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases