Differential anti-proliferative actions of peroxisome proliferator-activated receptor-γ agonists in MCF-7 breast cancer cells

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) activation has been a new approach to cancer therapy. In the present study, we investigated the effects of two structurally different PPAR gamma agonists, rosiglitazone and KR-62980 on MCF-7 breast cancer cells. Both agonists inhibited the cell proliferation and colony formation via apoptosis. PTEN expression was increased with decreased Akt phosphorylation by the agonists, whereas agonists actions were abolished in PTEN knockdown cells, indicating the critical role of PTEN in the anti-proliferative effects of PPAR gamma activation. Rosiglitazone induced the MCF-7 cell differentiation but KR-62980 did not alter the differentiation pattern with little effects on the lipid accumulation and the expression of lipogenesis markers. These results suggest that PPAR gamma activation may result in the inhibition of cell proliferation and/or induction of cell differentiation depending on the type of PPAR gamma agonists, and that KR-62980 may be useful in breast cancer therapy by inducing apoptosis. (c) 2006 Elsevier Inc. All rights reserved.