The Combination Effects of Phytoestrogens on Cell Proliferation, Cell Cycle Progression and Estrogen Receptor Alpha
CHINGWEN YING1*, JIH-TAY HSU2, CHUN-DA YANG1, SHIN-JAY HSUNG1, LU-KAI WANG1,
CHUN-MING LIN1 AND LONG-FANG OLIVER CHEN3
1. Department of Microbiology, Soochow University, Taipei, Taiwan, R.O.C.
2. Department of Animal Science, National Taiwan University, Taipei, Taiwan, R.O.C.
3. Institute of Botany, Academia Sinica, Taipei, Taiwan, R.O.C.
(Received: May 26, 2004; Accepted: November 22, 2004)
ABSTRACT
Phytoestrogens are plant chemicals that have been related to the occurrence of human breast cancers and other estrogen-dependent cancers. This study was designed to examine the potential combinational effects and estrogenic activity of phytoestrogens in MCF-7 human breast cancer cells. Results showed that the phytoestrogens biochanin A and daidzein inhibited the proliferation of MCF-7 cells in a dose-dependent manner. Both biochanin A and daidzein delayed the progression of the cell cycle from the G2/M phase to the G1 phase at growth inhibitory concentrations. Treatment with biochanin A down-regulated the level of estrogen receptor-alpha (ER-α) mRNA, but this down-regulation was not affected by the presence of the antiestrogen ICI182,780. When cells were treated with biochanin A at a growth inhibitory concentration of 40 μg/mL, co-administration of daidzein resulted in an enhanced inhibitory effect on the MCF-7 cell growth. In addition, neither the growth inhibition, nor the delayed cell cycle progression induced by biochanin A was affected by the addition of antiestrogen. These results suggest that the growth regulatory effects of phytoestrogens may be associated with cell cycle progression, and the underlying mechanism involves at least in part the modulation of a non classical ER-α signal
pathway.
Key words: phytoestrogen, fertility, estrogen receptor