Mitogenic activity of zeranol in human breast cancer cells is enhanced by leptin and suppressed by gossypol.

BACKGROUND: The molecular links between breast cancer and obesity have been studied for many years. Obesity significantly increases the incidence rate and chance of morbidity of breast cancer. Leptin, mainly secreted by adipocytes, plays an important role in breast cancer development. Leptin expression is up-regulated in obesity and it can promote breast cancer cell growth. Zeranol is used as an anabolic growth promoter to stimulate cattle growth in the U.S. beef industry. (-)-Gossypol, a natural polyphenolic compound extracted from cottonseed, is an anticancer chemopreventive agent. MATERIALS AND METHODS: Zeranol, leptin and (-)-gossypol were used to investigate MCF-7 Adr cell growth. RESULTS: Leptin enhanced the sensitivity of MCF-7 Adr cells to zeranol and increased cell growth. Exposure to zeranol may lead to initiation of transformation of normal breast cells to breast preneoplastic cells. CONCLUSION: It is suggested that obese individuals may be at greater risk of developing zeranol-induced breast cancer.

Tamoxifen prevents induction of hepatic neoplasia by zeranol, an estrogenic food contaminant.

Zeranol (alpha-zearalanol) is a beta-resorcylic acid lactone (RAL) that has estrogen activity. It is synthesized by molds and is difficult to avoid in human food products. We tested the ability of this mycoestrogen to damage the liver of the Armenian hamster, a rodent that is especially sensitive to hepatotoxic effects of exogenous estrogens. Zeranol induced acute hepatotoxicity and, subsequently, hepatic carcinogenesis; both effects were blocked by tamoxifen, suggesting estrogen receptor mediation. Because zeranol is acting alone as a primary initiator of hepatic neoplasms, this model provides an unusual opportunity to study the pathogenesis of estrogen-initiated tumorigenesis.