Abstract

BackgroundConjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues.MethodsThe localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction.ResultsThe results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam) and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA-MB-231 cells.ConclusionThese data, therefore, demonstrate that ERα plays important roles in CLA induced apoptosis in human breast tissues.

Highlights

  • Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems

  • E2-stimulated cell growth was suppressed by CLA or treated fetal bovine serum (FBS). 4-Hydroxytamoxifen (Tam), and the combination of CLA with Tam decreased the stimulative effects of E2 in the estrogen receptor D (ERD)(+) human breast cancer cell line, MCF-7 even further (Fig. 1A)

  • These results suggested that CLA may enhance the therapeutic efficiency of Tam in estrogen-responsive human breast cancer patients

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Summary

Introduction

Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Studies showed that beef CLA isomers even when associated with other beef fatty acids reduce human cancer cell growth [3] and beef tallow increases the potency of CLA against mouse mammary tumor metastasis [4]. CLA studies in our laboratory [5,6,7] demonstrated the anti-tumor effect of CLA (I) on angiogenesis by suppression of the predominant vascular endothelial growth factor (VEGF) isoforms, VEGF 121 and 165, and mRNA expression in a human breast cancer cell line; (II) via up-regulation of the estrogen-regulated cancer suppressor gene, protein tyrosine phosphatase J (PTPJ) in human breast cells; and (III) by modulation of prostaglandin E2 (PGE2) signaling in canine mammary cells. The American Society of Clinical Oncology (ASCO) Health Services

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