K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c.

The indole carbazole K252a has been shown in previous studies to inhibit the platelet-derived growth factor signal transduction pathway in gliomas. Because K252a has nonspecific effects on protein kinase function, we studied its effect on cyclin-dependent kinases (CDK) and cell cycle blockade in glioma cells. K252a blocked T98G cells at the G1/S and G2/M checkpoints. Consistent with cell cycle arrest, K252a was shown to hypophosphorylate Rb, upregulate p21, and decrease Cdc2 and Cdc25c activity. Finally, cell cycle arrest in T98G cells resulted in apoptosis as determined by cell morphology and DNA laddering. K252a is a useful tool for studying the effects of CDK inhibition and cell cycle blockade in tumor cells.