Biochemical pharmacology
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Biochemical pharmacology · Sep 2005
Effects of the cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) on the physiology of cultured human keratinocytes.
CYC202 (R-roscovitine) is a potent cyclin-dependent kinase inhibitor, investigated as a potential anti-cancer agent. The knowledge of the action of this pharmacological agent on normal human cells is still limited. In this study, we have explored the effects of the cyclin-dependent kinase inhibitor CYC202 on normal human epidermal keratinocytes. ⋯ These effects were strongly dependent on cell density and were observed only in highly proliferative keratinocytes. We concluded that CYC202 although highly potent against cancer cells inhibits also the proliferation and induces early apoptotic events in autocrine culture of normal human keratinocytes, activates p38 MAP kinase pathway and alters the expression of the epidermal differentiation markers. These results suggest that despite this potency against tumour cells, CYC202 must be used attentively in the clinical practice.