Breast cancer is a serious disease in the US. Numerous risk factors have been linked to this disease. The safety of using growth promoters, such as
zeranol, remains under debate due to the lack of sufficient in vitro and in vivo evidence. Using CellTiter 96(™) Aqueous Non-Radioactive Cell Proliferation assay, real-time PCR and Western blot analysis, we evaluated the effects of sera harvested from experimental and control heifers before and after one month of
zeranol implantation on the growth of human
breast cancer cell line MCF-7 as well as the involved mechanisms. We found that sera harvested from the heifers following one month of
zeranol implantation were more mitogenically potent in stimulating the proliferation of MCF-7 cells when compared to sera harvested from the same heifers before
zeranol implantation and the control heifers. Further investigation found that
dextran-coated
charcoal suppressed the stimulating effect of the sera on MCF-7 cell growth. The mechanisms involved in the MCF-7 cell proliferation stimulated by
zeranol-containing sera may include up-regulation of
cyclin D1 and down-regulation of p53 and p21 expression at the
mRNA and
protein levels in the cells. The results suggest that the consumption of beef products containing biologically active residues of
zeranol or its metabolites is a risk linked to
breast cancer development. Further investigation is required in order to clarify this critical issue.