Differential inhibition of fatty acid transport in tissue-isolated steroid receptor negative human breast cancer xenografts perfused in situ with isomers of conjugated linoleic acid.
In established rodent tumors and human cancer cell lines, conjugated dienoic isomers of linoleic acid (CLA) suppress the growth-stimulating effects of linoleic acid (LA) and its metabolism to the mitogenic agent, 13-hydroxyoctadecadienoic acid (13-HODE). Here, we compared the effects of three CLA isomers on LA uptake and metabolism, and growth in human breast xenografts perfused in situ in female nude rats. The results demonstrated that two CLA isomers [10t, 12c-CLA>9t, 11t-CLA] caused a dose-dependent inhibition of LA uptake, cAMP content, 13-HODE formation, Erk 1/2 activity, and [(3)H]thymidine incorporation into tumor DNA; 9c, 11t-CLA showed no effect. The inhibitory effect is reversible with either pertussis toxin (PTX) or 8-Br-cAMP suggesting that CLA isomers differentially inhibit LA uptake and metabolism and cell proliferation in human breast cancer in vivo via a receptor-mediated, PTX-sensitive pathway.
Dauchy
Robert T
RT
Bassett Research Institute, The Mary Imogene Bassett Hospital, One Atwell Road, Cooperstown, NY 13326, USA.
Dauchy
Erin M
EM
Sauer
Leonard A
LA
Blask
David E
DE
Davidson
Leslie K
LK
Krause
Jean A
JA
Lynch
Darin T
DT
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001692:Biological Transport; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D037342:Pertussis Toxin / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley
D000991:Antithrombins; D005227:Fatty Acids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D020033:Protein Isoforms; D015124:8-Bromo Cyclic Adenosine Monophosphate; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D000242:Cyclic AMP; D037342:Pertussis Toxin