Investigations on cellular proliferation induced by zearalenone and its derivatives in relation to the estrogenic parameters

Fiorenza Minervini, Alessandra Giannoccaro, Aldo Cavallini, Angelo Visconti

Research output: Contribution to journalArticlepeer-review

Abstract

Many man-made chemicals (pesticides) and naturally occurring compounds (mycotoxins and phytoestrogens) can enter the food chain and bind to estrogen receptors (ERs). Mycotoxins, including zearalenone (ZEA) and its derivatives, can occur worldwide in cereals and cause several health disorders. In order to characterize the estrogenic activity of zearalenone and its derivatives (α-zearalenol (α-ZEA), β-zearalenol (β-ZEA), α-zearalanol (α-ZAL) and β-zearalanol (β-ZAL)), the proliferation of ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was measured. After exposure at levels ranging from 0.1 pM to 0.1 μM, cell proliferation (E-screen assay) was evaluated by MTT test through estrogenic parameters. On the MCF-7 cell line, estrogenic concentration that induced 50% cellular proliferation (EC50) of β-zearalenol was statistically higher (5.2 × 10-3 μM) than those of other zearalenone-related compounds, in agreement with other authors. All mycotoxins showed similar estrogenic parameters, with the exception of α-zearalenol that induced a higher proliferative effect (PE = 2.6) and relative proliferative potency (RPP = 7). Since MCF-7 contains both ERα and ERβ-positive cells, at the mRNA and protein level, the estrogenic activity induced by mycotoxins may be ER-mediated, particularly through ERα that was the predominant ER subtype in these cells. A partial antagonism of mycotoxin-related estrogenic proliferation was seen when tamoxifen was used, confirming a receptor-dependent estrogenic response. MDA-MB-231 cells did not show ERs and after exposure to mycotoxins or 17β-estradiol marginal PE values related to growth variability of MDA-MB-231 were found. Further studies are needed to understand in human tissues the mechanisms of action of ZEA and its derivatives that may be found as contaminants in the human diet.

Original languageEnglish
Pages (from-to)272-283
Number of pages12
JournalToxicology Letters
Volume159
Issue number3
DOIs
Publication statusPublished - Dec 15 2005

Keywords

  • E-screen assay
  • Estrogens
  • MCF-7
  • MDA-MB-231
  • MTT test
  • Zearalenones

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Investigations on cellular proliferation induced by zearalenone and its derivatives in relation to the estrogenic parameters'. Together they form a unique fingerprint.

Cite this