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 [3H]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.