Pharmacological growth inhibition of papillomavirus type 16 E6E7-transformed keratinocytes by the CDK-Inhibitor CYC202

In the present study we have analysed the effect of the pharmacological CDK-inhibitor CYC202 on HPV16 E6- and E7-transformed human keratinocytes. The proliferation rates of E6E7 keratinocytes treated with CYC202 were determined by measurement the ³H-thymidine incorporation in the newly synthesised DNA molecules. The effect of CYC202 on some mitogen-activated protein kinases (MAPK) implicated in the regulation of cell proliferation, differentiation and apoptosis was also studied by Western blotting. CYC202 effectively inhibits the proliferation of E6E7 keratinocytes in a dose-dependent manner. Treatment with CYC202 strongly increases the activity of p38 MAP kinase and inhibits ERK1/2 at the highest concentration used. The phosphorylation of HSP27 and c-Myc are also changed in correlation with the upstream kinases from the MAPK family.