Conjugated Linoleic Acid (CLA) Modulates Prostaglandin E2 (PGE2) Signaling in Canine Mammary Cells

• Published in: Anticancer research Vol. 26; no. 2A; pp. 889 - 898
• Main Authors: Wang, Li-Shu, Huang, Yi-Wen, Liu, Suling, Chang, Hsiang-Lin, Ye, Weiping, Shu, Sherry, Sugimoto, Yasuro, Funk, Julie A, Smeaks, Daniel D, Hill, Lawrence N, Lin, Young C
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.03.2006
• Subjects: Animals; Biological and medical sciences; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 Inhibitors - pharmacology; Dinoprostone - metabolism; Dog Diseases - drug therapy; Dogs; Female; Linoleic Acids, Conjugated - pharmacology; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - metabolism; Medical sciences; Receptors, Prostaglandin E - antagonists & inhibitors; Receptors, Prostaglandin E - biosynthesis; Receptors, Prostaglandin E, EP2 Subtype; Signal Transduction - drug effects; Tumor Cells, Cultured; Tumors; Fissipedia; PGE2; Carnivora; Canine mammary; COX-2; Enzyme; Arachidonic acid derivatives; Cyclooxygenase 2; EP2; Polyunsaturated fatty acid; Prostaglandin E2; Lipids; Linoleic acid; Vertebrata; Mammalia; Cancerology; Signaling pathway; Eicosanoid; Animal; CLA; Oxidoreductases; Mammary gland; Dog
• ISSN: 0250-7005; 1791-7530

Background: Conjugated linoleic acid (CLA), a naturally occurring linoleic acid isomer found in ruminant-produced foods, has the potential to serve as an effective chemopreventive nutriceutical factor for breast cancer prevention based upon previous published studies. There are several CLA isomers in ruminant-produced food products, among which t10, c12-CLA and c9, t11-CLA are more potent. Expression of cyclooxygenase 2 (COX-2) in mammary tumors has been correlated with poor prognosis. Prostaglandin E 2 (PGE 2 ) is a major COX-2 product in various cancers and, as in humans, PGE 2 concentrations in canine tumor tissues were frequently elevated. Moreover, a PGE 2 receptor subtype, EP2, is highly expressed in mammary tumors. Thus, various studies have implicated the important role of PGE 2 and EP2 in COX-2-regulated tumor development. Materials and Methods: Mammary tumor and normal mammary tissues were both collected from a female dog with mammary tumor. Both malignant and normal mammary tissues were subjected to isolation of epithelial and stromal cells. The effects of t10, c12-CLA and c9, t11-CLA on proliferation, as well as COX-2 and EP2 protein expression in canine mammary normal and cancerous cells, were detected by CellTiter 96ì AQueous assay and Western blot assay, respectively. Results: Both t10, c12-CLA and c9, t11-CLA not only suppressed malignant mammary cell growth, but also exerted inhibitory effects on tumor-associated non-malignant mammary cells. Similarly, both t10, c12-CLA and c9, t11-CLA suppressed EP2 protein expression in both normal and malignant mammary cells. t10, c12-CLA was more effective in decreasing COX-2 protein expression in malignant mammary cells, while, in contrast, c9, t11-CLA down-regulated COX-2 protein expression in both normal and malignant mammary cells. Conclusion: The results indicate that the dietary component CLA regulates COX-2 and EP2 protein expression in both malignant mammary cells and cells from the tumor-associated stromal compartment. In turn, this may suppress PGE 2 signaling, leading to better prognosis. We further speculate that the knowledge obtained from canine studies may also be beneficial to study human breast cancer.