Article

Inhibition of estrogen receptor alpha expression and function in MCF-7 cells by kaempferol.

Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore.
Journal of Cellular Physiology (impact factor: 3.87). 03/2004; 198(2):197-208. DOI:10.1002/jcp.10398 pp.197-208
Source: PubMed

ABSTRACT Estrogens are mitogenic for estrogen receptor (ER)-positive breast cancer cells. Current treatment of ER-positive breast tumors is directed towards interruption of estrogen activity. We report that treatment of ER-positive breast cancer cells with kaempferol resulted in a time- and dose-dependent decrease in cell number. The concentration required to produce 50% growth inhibition at 48 h was approximately 35.0 and 70.0 microM for ER-positive and ER-negative breast cancer cells, respectively. For MCF-7 cells, a reduction in the ER-alpha mRNA equivalent to 50, 12, 10% of controls was observed 24 h after treatment with 17.5, 35.0, and 70.0 microM of kaempferol, respectively. Concomitantly, these treatments led to a 58, 80, and 85% decrease in ER-alpha protein. The inhibitory effect of kaempferol on ER-alpha levels was seen as early as 6 h post-treatment. Kaempferol treatment also led in a dose-dependent decrease in the expression of progesterone receptor (PgR), cyclin D1, and insulin receptor substrate 1 (IRS-1). Immunocytochemical study revealed that ER-alpha protein in kaempferol-treated MCF-7 cells formed an aggregation in the nuclei. Kaempferol also induced degradation of ER-alpha by a different pathway than that were observed for the antiestrogen ICI 182,780 and estradiol. Estradiol-induced MCF-7 cell proliferation and expression of the estrogen-responsive-element-reporter gene activity were abolished in cells co-treated with kaempferol. These findings suggest that modulation of ER-alpha expression and function by kaempferol may be, in part, responsible for its anti-proliferative effects seen in in vitro.

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    Haitao Luo, Bingbing Jiang, Bingyun Li, Zhaoliang Li, Bing-Hua Jiang, Yi Charlie Chen
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    Article: Sustained ERK activation is involved in the kaempferol-induced apoptosis of breast cancer cells and is more evident under 3-D culture condition.
    Bong-Woo Kim, Eung-Ryoung Lee, Hye-Min Min, Hyo-Soon Jeong, Jae-Yeon Ahn, Jung-Hyun Kim, Hye-Yeon Choi, Hana Choi, Eun Young Kim, Se Pill Park, Ssang-Goo Cho
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Keywords

50% growth inhibition
 
6 h post-treatment
 
cell number
 
Current treatment
 
ER)-positive breast cancer cells
 
ER-alpha expression
 
ER-alpha mRNA equivalent
 
ER-alpha protein
 
ER-negative breast cancer cells
 
ER-positive breast cancer cells
 
ER-positive breast tumors
 
Estradiol-induced MCF-7 cell proliferation
 
estrogen activity
 
estrogen receptor
 
estrogen-responsive-element-reporter gene activity
 
Estrogens
 
insulin receptor substrate 1
 
Kaempferol treatment
 
kaempferol-treated MCF-7 cells
 
progesterone receptor
 

Huynh Hung