Conjugated linoleic acid (CLA), found naturally in dairy products and ruminant meats, refers to isomers of octadecadienoic acid with conjugated double bonds. CLA inhibits both DMBA- and NMU-induced rat mammary carcinogenesis, and its antitumor efficacy is similar whether it is fed only during puberty, or continuously during promotion. Pubertal feeding is associated with a reduced proliferation of the epithelial cells within the terminal end buds (TEBs) and lobular epithelium, and results in a decrease in the epithelial density, suggesting a reduction in the carcinogen-sensitive target population. During promotion, CLA feeding induces apoptosis of preneoplastic lesions. The effects of CLA are mediated by a direct action on the epithelium, as well as by an indirect effect through the stroma. CLA is incorporated into the neutral lipids of mammary adipocytes, where it can serve as a local reservoir of CLA. Additionally, CLA induces the adipogenic differentiation of multipotent mammary stromal cells in vitro, and inhibits their development into three-dimensional capillary networks. This suggested that CLA might inhibit angiogenesis in vivo, a hypothesis that was subsequently confirmed. The antiangiogenic effect is mediated, in part, through a CLA-induced decrease in serum VEGF (vascular endothelial growth factor) and mammary gland VEGF and flk-1. Together, the data suggest that CLA may be an excellent candidate for prevention of breast cancer.
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