title: Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture.
abstract: The trace fatty acid conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis when fed prior to carcinogen during pubertal mammary gland development or during the promotion phase of carcinogenesis. The following studies were done to investigate possible mechanisms of these effects. Using a physiological model for growth and differentiation of normal rat mammary epithelial cell organoids (MEO) in primary culture, we found that CLA, but not linoleic acid (LA), inhibited growth of MEO and that this growth inhibition 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 epithelial protein kinase C (PKC) since neither total activity nor expression nor localization of PKC isoenzymes alpha, beta II, delta, epsilon, eta, or zeta were altered in the epithelium of CLA-fed rats. In contrast, PKCs delta, epsilon, and eta were specifically upregulated and associated with a lipid-like, but acetone-insoluble, fibrillar material found exclusively in adipocytes 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 epithelial density and to inhibit the outgrowth of initiated MEO. Moreover, the changes in mammary adipocyte PKC expression and lipid composition suggest that the adipose stroma may play an important in vivo role in mediating the ability of CLA to inhibit mammary carcinogenesis.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA. mip@sc3101.med.buffalo.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Ip
authors.forename: P A
authors.initials: PA
authors.lastname: Masso-Welch
authors.forename: S F
authors.initials: SF
authors.lastname: Shoemaker
authors.forename: W K
authors.initials: WK
authors.lastname: Shea-Eaton
authors.forename: C
authors.initials: C
authors.lastname: Ip
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004041:Dietary Fats / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D007536:Isomerism; D008041:Linoleic Acids / Q000378:metabolism / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D009940:Organoids / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016588:Anticarcinogenic Agents; D004041:Dietary Fats; D007527:Isoenzymes; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C046938:9,11-linoleic acid; D004247:DNA; C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; C497256:Prkce protein, mouse; C497257:Prkce protein, rat; C081975:protein kinase C eta; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon