Genistein inversely affects tubulin-binding agent-induced apoptosis in human breast cancer cells

Cho Hwa Liao, Shiow Lin Pan, Jih Hwa Guh, Che Ming Teng

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Genistein, a natural isoflavone phytoestrogen present in soybeans, has been extensively studied as a chemopreventive or therapeutic agent in several types of cancer. The traditional Asian diet is rich in soy products may explain in part why the incidence of breast cancer in Asian women is relatively low. To improve therapeutic benefits, we investigated the combination of genistein with chemotherapeutic agents in phenotypically dissimilar human breast cancer cells, MCF-7 and MDA-MB-231, in which estrogen receptor expression is positive and negative, respectively. In the present study, genistein significantly decreased cell apoptosis induced by tubulin-binding agents, paclitaxel and vincristine. FACScan analysis revealed that genistein also diminished the accumulation of the G2/M phase in the cell cycle caused by tubulin-binding agents. In situ staining of microtubules revealed that genistein could decrease paclitaxel-induced tubulin polymerization. However, in vivo tubulin polymerization assay revealed that simultaneous treatment of genistein did not change the tubulin/microtubule dynamic. Genistein reduced Bcl-2 phosphorylation triggered by paclitaxel and vincristine without changing Bax protein expression. p53 and p21 expression, monitored by Western blotting, was not altered by genistein. However, the expression of cyclin B1 and CDC2 kinase was markedly decreased in combination with genistein. In conclusion, genistein inversely affected tubulin-binding agent-induced apoptosis via down-regulation of cyclin B1/CDC2 kinase expression resulting in reduced Bcl-2 phosphorylation.

Original languageEnglish
Pages (from-to)2031-2038
Number of pages8
JournalBiochemical Pharmacology
Volume67
Issue number11
DOIs
Publication statusPublished - Jun 1 2004
Externally publishedYes

Fingerprint

Genistein
Tubulin
Cells
Apoptosis
Breast Neoplasms
Paclitaxel
Cyclin B1
Phosphorylation
Vincristine
Microtubules
Polymerization
Phosphotransferases
Phytoestrogens
bcl-2-Associated X Protein
Isoflavones
G2 Phase
MCF-7 Cells
Nutrition
Soybeans
Estrogen Receptors

Keywords

  • CDC2 kinase
  • Cyclin B1
  • Genistein
  • Paclitaxel
  • Vincristine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Genistein inversely affects tubulin-binding agent-induced apoptosis in human breast cancer cells. / Liao, Cho Hwa; Pan, Shiow Lin; Guh, Jih Hwa; Teng, Che Ming.

In: Biochemical Pharmacology, Vol. 67, No. 11, 01.06.2004, p. 2031-2038.

Research output: Contribution to journalArticle

Liao, Cho Hwa ; Pan, Shiow Lin ; Guh, Jih Hwa ; Teng, Che Ming. / Genistein inversely affects tubulin-binding agent-induced apoptosis in human breast cancer cells. In: Biochemical Pharmacology. 2004 ; Vol. 67, No. 11. pp. 2031-2038.
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