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  • Title: Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine.
    Author: Song Y, Kesuma D, Wang J, Deng Y, Duan J, Wang JH, Qi RZ.
    Journal: Biochem Biophys Res Commun; 2004 Apr 23; 317(1):128-32. PubMed ID: 15047157.
    Abstract:
    As key regulators of the cell proliferation cycle, cyclin-dependent kinases (CDKs) are attractive targets for the development of anti-tumor drugs. In the present study, harmine was identified from a collection of herbal compounds to be a specific inhibitor of Cdk1/cyclin B, Cdk2/cyclin A, and Cdk5/p25 with IC50 values at low micromoles. It displayed little effect on other serine/threonine and tyrosine kinases tested. The CDK inhibition by harmine is competitive with ATP-Mg2+, suggesting that it binds to the ATP-Mg2+-binding pocket of CDKs. In cytotoxicity assays, harmine exhibited a strong inhibitory effect on the growth and proliferation of carcinoma cells whereas it had no significant effect on quiescent fibroblasts. Further, harmine was found to block DNA replication in the carcinoma cells. Taken together, harmine is a selective inhibitor of CDKs and cell proliferation.
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