Agonistic and Antagonistic effects of Zearalenone, an Etrogenic Mycotoxin, Human Cancer Cell lines

Withanage GS, Murata H, Koyama T, Ishiwata I.

Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by the molds Fusarium graminearium and Fusarium culmorum found in a variety of host plants and soil debris around the world. ZEA is usualy non-lethal to animals but is important to livestock producers because its hyperestrogenic effects adversely influence the reproductive performance of animals. There have been suggestions of possible involvement of ZEA in the progression of breast malignancies and tumors of the female reproductive tract in humans. The toxic or stimulatory effects of ZEA and its metabolites alpha-zearalenol and 17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol (100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and alpha-zearalenol stimulated the proliferation of SKN and HHUA cells. On HepG2 cells, lower concentrations (10 nM) of 17-beta-estradiol and higher concentrations (100 microM) of ZEA exhibited toxic effects, whereas treatment with higher concentrations of 17-beta-estradiol and lower concentration of ZEA did not show toxic effects. A dose dependent antagonistic effect was observed when the cell cultures were pre-incubated with ICI 182,780, a synthetic estrogen receptor blocker, before estradiol or mycotoxin treatments.