Conjugated Linoleic Acid Blocks Estrogen Signaling in Human Breast Cancer Cells

Abstract

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid found in dairy products and meat from ruminants, has been widely shown to possess anticarcinogenic activity against breast cancer both in vitro and in animal models. However, little information is available concerning the mechanisms of the antitumor effects of these compounds. In this study, we investigated whether CLA has direct antiestrogenic activity in estrogen receptor positive (ER+) breast cancer cells. Treatment of the ER+ cell line, MCF-7, with 5 purified CLA isomers as well as "mixed" CLA showed a dose-dependent growth inhibition with the 9cis,11cis and 9cis,11trans being the most and least potent isomers, respectively. In assessing effects on a number of variables that play obligatory roles in the estrogen signaling pathway, we determined that CLA treatment downregulated ERalpha expression at both mRNA and protein levels and decreased binding activity of nuclear protein to a canonical estrogen response element (ERE(v)). Using a reporter gene construct (ERE(v)-tk-Luc) that was transiently transfected into MCF-7 cells, we also demonstrated inhibition of promoter activity by CLA that was directly mediated by blockage of activity through the ERE. The results indicated that the order of potency of the CLA isomers for inhibiting activation of ERE(v) was similar to that demonstrated for their antiproliferative activity on MCF-7 cells. Taken together, these findings demonstrate that CLA compounds possess potent antiestrogenic properties that may at least partly account for their antitumor activity on breast cancer cells.

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

“…Taken together, these data lead us to conclude that the most physiologically important anti-aromatase phytochemical in mushrooms is conjugated linoleic acid or its derivatives. In addition to its action as an aromatase inhibitor, conjugated linoleic acid has been reported to modulate estrogen receptor function, leading to the suppression of proliferation in MCF-7 cells (43,44). Liu and Sidell (45) have shown that conjugated linoleic acid can also modulate estrogen receptor phosphorylation and, therefore, activity.…”

Characterization of volatile compounds of <i>Albertisia papuana</i> Becc root extracts and cytotoxic activity in breast cancer cell line T47D

“…Various studies have reported that has biological beneficial effects, including anticancer activity. LA inhibits the initiation, promotion, and progression phases in mammary tumors [14].In addition, LA showed anticancer activity [16], especially by its antiproliferative activity [17] and by inducing apoptosis in breast cancer cells [18].LA was demonstrated to not only inhibit the growth of hepatoma cell but also induce apoptosis in colorectal cell line [19,20]. A study of human leukemic cells MOLT-4 showed that palmitic acid inhibited DNA topoisomerase I and induced apoptosis [20], however in human lung adenocarcinoma cell line A549, palmitic acid only inhibited DNA topoisomerase I without inducing apoptosis [21].…”

The Role of Conjugated Linoleic Acid in Breast Cancer Growth and Development

“…CLA treatment of MCF-7 breast cancer cells was shown to increase protein levels of the anti-proliferative PPARγ and decrease protein levels of the anti-apoptotic PPARβ/δ [67,68]. CLA also increased the localization of PPARγ from the cytosol to the nucleus, and increased PPAR response element activation [68,69]. Use of a PPARγ antagonist abolished the growth inhibitory effects of CLA [68].…”