Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21

Nutr Cancer. 2007;59(1):115-9. doi: 10.1080/01635580701419030.


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 p21(Cip1) 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 p57(Kip2). Taken together, our data suggest for the first time that the regulation of CDK4 and p21(Cip1)1 may participate in the anticancer activity pathway of hesperetin in MCF-7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / prevention & control*
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase / drug effects*
  • Hesperidin / pharmacology*
  • Humans
  • Time Factors


  • Cyclin-Dependent Kinase Inhibitor p21
  • Hesperidin
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • hesperetin