Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture

The trace fatty acid conjugated linoleic acid (CLA) inhibits rat mammary ca rcinogenesis when fed prior to carcinogen during pubertal mammary gland dev elopment or during the promotion phase of carcinogenesis. The following stu dies were done to investigate possible mechanisms of these effects. Using a physiological model for growth and differentiation of normal rat mammary e pithelial cell organoids (MEO) in primary culture, we found that CLA, but n ot linoleic acid (LA), inhibited growth of MEO and that this growth inhibit ion was mediated both by a reduction in DNA synthesis and a stimulation of apoptosis. The effects of CLA did not appear to be mediated by changes in e pithelial protein kinase C (PKC) since neither total activity nor expressio n nor localization of PKC isoenzymes alpha, beta II, delta, epsilon, eta, o r zeta were altered in the epithelium of CLA-fed rats, in contrast, PKCs de lta, epsilon, and eta were specifically upregulated and associated with a l ipid-like, but acetone-insoluble, fibrillar material found exclusively in a dipocytes from CLA-fed rats. Taken together, these observations demonstrate that CLA can act directly to inhibit growth and induce apoptosis of normal MEO and may thus prevent breast cancer by its ability to reduce mammary ep ithelial density and to inhibit the outgrowth of initiated MEG. Moreover, t he changes in mammary adipocyte PKC expression and lipid composition sugges t that the adipose stroma may play an important in vivo role in mediating t he ability of CLA to inhibit mammary carcinogenesis. (C) 1999 Academic Pres s.