Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells

Takashi Yuri, Reiko Tsukamoto, Katsuaki Miki, Norihisa Uehara, Yoichiro Matsuoka, Airo Tsubura

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Abstract

Zeranol (α-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.

Original languageEnglish
Pages (from-to)1307-1312
Number of pages6
JournalOncology reports
Volume16
Issue number6
Publication statusPublished - Dec 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yuri, T., Tsukamoto, R., Miki, K., Uehara, N., Matsuoka, Y., & Tsubura, A. (2006). Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells. Oncology reports, 16(6), 1307-1312.