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Original Articles

Hesperetin Induced G1-Phase Cell Cycle Arrest in Human Breast Cancer MCF-7 Cells: Involvement of CDK4 and p21

Pages 115-119 | Received 14 Jan 2007, Accepted 27 Mar 2007, Published online: 05 Dec 2007
 

Abstract

This study was to investigate the effects of hesperetin on cell proliferation and cell cycle arrest and explored the mechanism for these effects in breast carcinoma MCF-7 cells. Hesperetin significantly inhibited cell proliferation in a dose-dependent manner after treatment for 48 and 72 h and resulted in significant cell cycle arrest in the G1 phase. In the G1-phase related proteins, hesperetin downregulates the cyclin-dependent kinases (CDKs) and cyclins and upregulates p21Cip1 and p27 Kip1 in cells treated with hesperetin for 48 h and 72 h. After 72 h treatment, these phenomenons were more pronounced. Hesperetin treatment at high concentration for 72 h resulted in a decrease in CDK2 and CDK4 together with cyclin D. In addition, hesperetin increases the binding of CDK4 with p21 Cip1 but not p27 Kip1 or p57K ip2 . Taken together, our data suggest for the first time that the regulation of CDK4 and p21 Cip1 may participate in the anticancer activity pathway of hesperetin in MCF-7 cells.

Acknowledgments and Notes

This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, KRF–2006–311–F00127).

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