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

J. A. Choi, J. Y. Kim, J. Y. Lee, C. M. Kang, Ho Jeong Kwon, Y. D. Yoo, T. W. Kim, Y. S. Lee, S. J. Lee

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)837-844
Number of pages8
JournalInternational journal of oncology
Volume19
Issue number4
Publication statusPublished - 2001 Jan 1

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Quercetin
Cell Cycle Checkpoints
Cyclin B1
Cell Division
Apoptosis
Breast Neoplasms
Flavonoids
Cell Cycle
Phosphotransferases
Growth
Mitotic Index
G2 Phase
MCF-7 Cells
Up-Regulation
Staining and Labeling
Cell Line
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Choi, J. A., Kim, J. Y., Lee, J. Y., Kang, C. M., Kwon, H. J., Yoo, Y. D., ... Lee, S. J. (2001). Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. International journal of oncology, 19(4), 837-844.
Choi, J. A. ; Kim, J. Y. ; Lee, J. Y. ; Kang, C. M. ; Kwon, Ho Jeong ; Yoo, Y. D. ; Kim, T. W. ; Lee, Y. S. ; Lee, S. J. / Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. In: International journal of oncology. 2001 ; Vol. 19, No. 4. pp. 837-844.
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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.",
author = "Choi, {J. A.} and Kim, {J. Y.} and Lee, {J. Y.} and Kang, {C. M.} and Kwon, {Ho Jeong} and Yoo, {Y. D.} and Kim, {T. W.} and Lee, {Y. S.} and Lee, {S. J.}",
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Choi, JA, Kim, JY, Lee, JY, Kang, CM, Kwon, HJ, Yoo, YD, Kim, TW, Lee, YS & Lee, SJ 2001, 'Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin.', International journal of oncology, vol. 19, no. 4, pp. 837-844.

Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. / Choi, J. A.; Kim, J. Y.; Lee, J. Y.; Kang, C. M.; Kwon, Ho Jeong; Yoo, Y. D.; Kim, T. W.; Lee, Y. S.; Lee, S. J.

In: International journal of oncology, Vol. 19, No. 4, 01.01.2001, p. 837-844.

Research output: Contribution to journalArticle

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T1 - Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin.

AU - Choi, J. A.

AU - Kim, J. Y.

AU - Lee, J. Y.

AU - Kang, C. M.

AU - Kwon, Ho Jeong

AU - Yoo, Y. D.

AU - Kim, T. W.

AU - Lee, Y. S.

AU - Lee, S. J.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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.

AB - 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.

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