The PPARγ antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARγ-dependent and -independent mechanisms

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is overexpressed in many types of cancer, including breast cancer, and it is regulated by ligand binding and post-translational modifications. It was previously demonstrated that endogenous transactivation promotes an aggressive phenotype of malignant breast cells. This study examines whether selective antagonism of PPARγ with T0070907 is a potential strategy for breast cancer therapy. Materials and Methods: PPARγ activation was inhibited using both pharmacological and molecular approaches and proliferation, apoptosis, migration and invasion were measured in MDA-MB-231 and MCF-7 breast cancer cells. Results: T0070907 treatment inhibited proliferation, invasion and migration but did not significantly affect apoptosis. Molecular inhibition using a dominant negative (Δ462) receptor yielded similar results. T007 also mediated a dose-dependent decrease in phosphorylation of PPARγ, and its ability to bind to DNA, and may directly affect mitogen-activated protein kinase signaling. Conclusion: These data indicate that inhibiting endogenous PPARγ signaling may be a promising new approach to breast cancer therapy.