Leukotoxin diols from ground corncob bedding disrupt estrous cyclicity in rats and stimulate MCF-7 breast cancer cell proliferation.
Previous studies in our laboratory demonstrated that high-performance liquid chromatography (HPLC) analysis of ground corncob bedding extracts characterized two components (peak I and peak II) that disrupted endocrine function in male and female rats and stimulated breast and prostate cancer cell proliferation in vitro and in vivo. The active substances in peak I were identified as an isomeric mixture of 9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid, collectively designated tetrahydrofurandiols (THF-diols). Studies presented here describe the purification and identification of the HPLC peak II component as 9,10-dihydroxy-12-octadecenoic acid (leukotoxin diol; LTX-diol), a well-known leukotoxin. A synthetic mixture of LTX-diol and 12,13-dihydroxy-9-octadecenoic acid (iso-leukotoxin diol; i-LTX-diol) isomers was separated by HPLC, and each isomer stimulated (p < 0.001) MCF-7 cell proliferation in an equivalent fashion. The LTX-diol isomers failed to compete for [3H]estradiol binding to the estrogen receptor or nuclear type II sites, even though oral administration of very low doses of these compounds (>> 0.8 mg/kg body weight/day) disrupted estrous cyclicity in female rats. The LTX-diols did not disrupt male sexual behavior, suggesting that sex differences exist in response to these endocrine-disruptive agents.
Markaverich
Barry M
BM
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. barrym@bcm.tmc.edu
Crowley
Jan R
JR
Alejandro
Mary A
MA
Shoulars
Kevin
K
Casajuna
Nancy
N
Mani
Shaila
S
Reyna
Andrea
A
Sharp
John
J
D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D006799:Housing, Animal; D006801:Humans; D008297:Male; D008934:Mitogens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011959:Receptors, Estradiol / Q000378:metabolism; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013229:Stearic Acids / Q000378:metabolism / Q000633:toxicity*; D014316:Tritium; D003313:Zea mays / Q000737:chemistry
C120038:9,10-dihydroxy-12-octadecenoic acid; D008934:Mitogens; D011959:Receptors, Estradiol; D013229:Stearic Acids; D014316:Tritium