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

Citation
Ja. Choi et al., Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin, INT J ONCOL, 19(4), 2001, pp. 837-844
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
1019-6439 → ACNP
Volume
19
Issue
4
Year of publication
2001
Pages
837 - 844
Database
ISI
SICI code
1019-6439(200110)19:4<837:IOCCAA>2.0.ZU;2-V
Abstract
Quercetin, a widely distributed bioflavonoid, has been shown to induce grow th inhibition in certain cancer cell types. In the present study we have pu rsued 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 clea rly showed that cells were transiently accumulated in M phase, 24 h after t reatment. 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 o f M phase. Levels of cyclin B1 and cyclin BI-associated Cdc2 kinase activit y were also decreased. We also found that quercetin markedly increased Cdk- inhibitor p21(CIP1/WAF1) protein level after treatment for 48 h or longer, and the induction of p21(CIP1/WAF1) increased its association with Cdc2-cyc lin B1 complex, however, up-regulation of p53 by quercetin was not observed . Quercetin also induced significant apoptosis in MCF-7 cells in addition t o cell cycle arrest, and the induction of apoptosis was markedly blocked by antisense p21(CIP1/WAF1) expression. The present data, therefore, demonstr ate that a flavonoid quercetin induces growth inhibition in the human breas t carcinoma cell line MCF-7 through at least two different mechanisms; by i nhibiting cell cycle progression through transient M phase accumulation and subsequent G2 arrest, and by inducing apoptosis.