Rosiglitazone Shows Sequence-Specific Synergy With Chemotherapeutic Drugs in Inhibition of McF-7 Breast Cancer Cell Line

Abstract

Preclinical studies have shown that peroxisome proliferator-activated receptor γ (PPARγ) ligands such as thiazolidinediones (TZDs) can exert antitumor effects against breast cancer and a variety of other cancers. In this study, we investigated the potential of repurposing a PPARγ ligand, rosiglitazone (RGZ), in combination with either of three chemotherapeutic agents, doxorubicin (Dox) or cisplatin (Cis) or 5-fluorouracil (5-FU), for the in-vitro treatment of breast cancer cell line, MCF-7. RGZ augmented the growth inhibition effect of Cis and 5-FU on MCF-7 cells. The synergy was observed only when chemotherapy preceded RGZ and not vice versa, demonstrating a sequence-specific effect. We also observed that the first administered drug gave its cell cycle pattern and apoptosis/necrosis pattern to the subsequently applied drug. Besides, no adipose differentiation in the form of lipid droplet accumulation was induced in treated cells regardless of the used drugs and their sequence of application. Together, our data show a synergistic effect of administering RGZ after Cis or 5-FU and suggests an inhibitory role of RGZ on the chemo-resistant MCF-7 side-populations.