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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Inhibition of cell-cycle progression in HeLa cells by HY52, a novel cyclin-dependent kinase inhibitor isolated from Bauhinia forficata.

In the course of screening for a novel inhibitor of cyclin-dependent kinase (CDK), HY52 (C17H30O2N2; molecular weight 294) was isolated from the leaves of Pata de Vaca (Bauhinia forficata). The growth of HeLa cells was inhibited in a dose-dependent manner when treated with 0.07 to 0.41 mM of HY52 for 24 h (IC50:0.11 mM). Furthermore, HY52 showed the selective inhibitory activity on CDC2 kinase purified using immunoprecipitation with an IC 50 value of 0.45 mM. A flow cytometric analysis of the HeLa cells treated with HY52 revealed an appreciable cell-cycle arrest in the G1 phase. Moreover, a TUNEL assay exhibited the apoptotic induction of HeLa cells treated with HY52. To obtain further information on the cell-cycle arrest induced by HY52, the expression of certain cell-cycle-associated proteins was examined using a Western blot analysis. The results revealed that HY52 was found to inhibit the proliferation of HeLa cells through inducing a G1-phase arrest by inhibiting pRb phosphorylation via an up-regulation of p21WAF1/CIP1 and p27KIP1, and G2/M-phase arrest by down-regulation of CDC2, cyclin A, and cyclin B1.[1]


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