Conjugated linoleic acid (CLA) modulates prostaglandin E2 (PGE2) signaling in canine mammary cells

Abstract

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 E2 (PGE2) is a major COX-2 product in various cancers and, as in humans, PGE2 concentrations in canine tumor tissues were frequently elevated. Moreover, a PGE2 receptor subtype, EP2, is highly expressed in mammary tumors. Thus, various studies have implicated the important role of PGE2 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 96 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 PGE2 signaling, leading to better prognosis. We further speculate that the knowledge obtained from canine studies may also be beneficial to study human breast cancer.