Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin

Int J Oncol. 2001 Oct;19(4):837-44. doi: 10.3892/ijo.19.4.837.

Abstract

Quercetin, a widely distributed bioflavonoid, has been shown to induce growth inhibition in certain cancer cell types. In the present study we have pursued the mechanism of growth inhibition in MCF-7 human breast cancer cells. Quercetin treatment resulted in the accumulation of cells specifically at G2/M phase of the cell cycle. Mitotic index measured by MPM2 staining clearly showed that cells were transiently accumulated in M phase, 24 h after treatment. The transient M phase accumulation was accompanied by a transient increase in the levels of cyclin B1 and Cdc2 kinase activity. However, 24 h or longer treatment caused a marked accumulation of cells in G2 instead of M phase. Levels of cyclin B1 and cyclin B1-associated Cdc2 kinase activity were also decreased. We also found that quercetin markedly increased Cdk-inhibitor p21CIP1/WAF1 protein level after treatment for 48 h or longer, and the induction of p21CIP1/WAF1 increased its association with Cdc2-cyclin B1 complex, however, up-regulation of p53 by quercetin was not observed. Quercetin also induced significant apoptosis in MCF-7 cells in addition to cell cycle arrest, and the induction of apoptosis was markedly blocked by antisense p21CIP1/WAF1 expression. The present data, therefore, demonstrate that a flavonoid quercetin induces growth inhibition in the human breast carcinoma cell line MCF-7 through at least two different mechanisms; by inhibiting cell cycle progression through transient M phase accumulation and subsequent G2 arrest, and by inducing apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antisense Elements (Genetics) / pharmacology
  • Apoptosis / drug effects*
  • Bisbenzimidazole
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects*
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Precipitin Tests
  • Quercetin / therapeutic use*
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antisense Elements (Genetics)
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Quercetin
  • Cyclin-Dependent Kinases
  • Bisbenzimidazole