Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells.
Zeranol (alpha-zearalanol) is a metabolite of the mycoestrogen zearalenone, and is used as a growth promoter of livestock due to its strong estrogenic activity. In the present study, we investigated the effects of zeranol on the growth of estrogen receptor (ER)-positive and -negative human breast carcinoma cells in vitro, and the molecules involved. At low concentrations, zeranol accelerated the growth of ER-positive MCF-7 and KPL-1 human breast carcinoma cells, but did not affect the growth of ER-negative MDA-MB-231 cells. At high concentrations, zeranol suppressed the growth of both ER-positive and -negative human breast carcinoma cells. The acceleration of ER-positive cell growth by low-dose zeranol involved the down-regulation of p21Cip1 (a cyclin-dependent kinase inhibitor), which resulted in cell cycle progression. High-dose zeranol induced the formation of a sub-G1 fraction and the up-regulation of the apoptosis stimulator p53, suggesting the induction of apoptosis. Thus, zeranol exerted dose-dependent biphasic effects on ER-positive human breast carcinoma cells, accelerating cell growth at low concentrations and inducing apoptosis at high concentrations.
Yuri
Takashi
T
Department of Pathology II, Kansai Medical University, Osaka 570-8506, Japan.
Tsukamoto
Reiko
R
Miki
Katsuaki
K
Uehara
Norihisa
N
Matsuoka
Yoichiro
Y
Tsubura
Airo
A
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects; D015029:Zeranol / Q000494:pharmacology*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D015029:Zeranol