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

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.

• Authors: J A Choi, J Y Kim, J Y Lee, C M Kang, H J Kwon, Y D Yoo, T W Kim, Y S Lee, S J Lee
• Journal: International journal of oncology (Int J Oncol) Vol. 19 Issue 4 Pg. 837-44 (Oct 2001) ISSN: 1019-6439 [Print] Greece
• PMID: 11562764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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