• Proceedings of the PSK Conference
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• 2002.10a
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• pp.336.3-337
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• 2002

We previously reported that a synthetic naphthoquinone analog. 2.3-dichloro-5.8-dihydroxy-1, 4-naphthoquinone (NA). effectively induces apoptosis in human leukemic HL-60 cells. However. the cellular mechanism by which NA induces cell death remain unclear. In this study. we show that NA induces activation of capases. release of cytochrome c and upregulation of proapoptotic Bax protein. Futhermore. NA suppressed phosphorylation of Akt and Bad. suggesting that Akt regulates NA-induced apoptosis. Expresson of a dominant negative Akt enhancde NA-induced apoptosis. suggesting that naphthoquinone analog induces apoptosis through activating proapoptotic pathway and by the inactivation of antiapoptotic pathway.

• Animal cells and systems
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• v.11 no.1
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• pp.9-15
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• 2007

The naphthoquinone analog (2,3-dichloro-6,9-dihydroxy-1,4-naphtoquinone, NA) has an inhibitory effect on cdc25A protein phosphatase in vitro, which is responsible for G1/S transition during cell cycle. However, the exact mechanism inducing the growth inhibition is not understood. In this study, we investigated the regulatory mechanisms of growth arrest induced by NA, as a new potent inhibitor of cdc25A phosphatase, in human hepatocarcinoma SK-hep-1 cells. We found that NA induced the G1 arrest by perturbation of protein tyrosine dephosphorylation of Cdk2, which may be resulting from inhibition of cdc25A phosphatase. In addition, p21 was expressed in a p53-independent manner and participated in the NA-induced G1 arrest by inhibiting Cdk2 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 arrest via inhibition of cdc25A and induction of p53-independent p21 expression in SK-Hep-1 cells.