Naphthoquinone Analog-induced G1 Arrest is Mediated by cdc25A Inhibition and p53-independent p21 Induction in Human Hepatocarcinoma Cells

초록

The naphthoquinone analog (2,3-dichloro-6,9-dihydroxy-1,4-naphtoquinone, NA) has an inhibitory effecton cdc25A protein phosphatase in vitro, which is responsiblefor G1/S transition during cell cycle. However, the exactmechanism inducing the growth inhibition is not understood.In this study, we investigated the regulatory mechanisms ofgrowth arrest induced by NA, as a new potent inhibitor ofcdc25A phosphatase, in human hepatocarcinoma SK-hep-1cells. We found that NA induced the G1 arrest by perturbationof protein tyrosine dephosphorylation of Cdk2, which maybe resulting from inhibition of cdc25A phosphatase. Inaddition, p21 was expressed in a p53-independent mannerand participated in the NA-induced G1 arrest by inhibitingCdk2 activity. Although the exact mechanism is not known,the p21 expression might be related to MAPK activation.From these results, we suggest that NA induces G1 arrestvia inhibition of cdc25A and induction of p53-independentp21 expression in SK-Hep-1 cells.

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