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.


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.


CONCLUSIONS
It is suggested that obese individuals may be at greater risk of developing zeranol-induced breast cancer.
Xu
Pingping
P
College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Ye
Weiping
W
Jen
Robert
R
Lin
Shu-Hong
SH
Kuo
Chieh-Ti
CT
Lin
Young C
YC
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000187:drug effects*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D015029:Zeranol / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D015029:Zeranol; D006072:Gossypol