CHOI Jung-A ⁽¹⁾ ; KIM Ja-Young ⁽¹⁾ ; LEE Jeong-Yim ⁽²⁾ ; KANG Chang-Mo ⁽¹⁾ ; KWON Ho-Jeong ⁽³⁾ ; YOO Young-Do ⁽¹⁾ ; KIM Tae-Whan ⁽¹⁾ ; LEE Yun-Sil ⁽¹⁾ ; LEE Su-Jae ⁽¹⁾

⁽¹⁾ Laboratory of Radiation Effect, Korea Cancer Center Hospital, Seoul 139-706, COREE, REPUBLIQUE DE
⁽²⁾ Department of Biological Sciences, Ajou University, Suwon 442-749, COREE, REPUBLIQUE DE
⁽³⁾ Department of Bioscience and Biothechnology, Sejong University, Seoul 143-747, COREE, REPUBLIQUE DE

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 B 1 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 Bl and cyclin B1-associated Cdc2 kinase activity 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-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 p21^CIP1/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.