A red onion peel-derived PPARγ inhibitor suppresses BPA-induced DNA synthesis and lipid accumulation in mesenchymal stem cells and mesenchymal-rich cancer cells.

Abstract

This study examined obesity- and insulin-associated gene expression, newly synthesised DNA (a measure of survival following mitosis), lipid accumulation (integral to cell differentiation), and chronic inflammatory soluble factors, including transforming growth factor β (TGFβ), interleukin-6 (IL-6), and chemokine CC-motif ligand-2 (CCL2), in the conditioned medium of three cell groups. The groups were: bisphenol A (BPA)-treated bone marrow-derived mesenchymal stem cells (BMSCs) only; BPA-treated BMSCs cultured in medium containing MK886 [a proliferator-activated receptor-gamma (PPARγ) inhibitor]; and BPA-treated BMSCs cultured in medium containing F1 (a potential PPARγ inhibitor). The results demonstrated that 25 μg/ml BPA induced optimal expression of the PPARγ transcript in BMSCs and that this effect persisted for 10 d. However, F1 reduced PPARγ transcript levels in BPA-treated BMSCs more effectively than MK886. In contrast, F1 was less effective than MK886 in regulating glucose transporter 4 (GLUT4) and perilipin transcript levels in BPA-treated BMSCs. F1 also showed the ability to inhibit DNA synthesis in BPA-treated BMSCs, implying that F1 may prevent BPA-induced proliferation in BMSCs. Notably, F1 exhibited greater inhibitory activity than MK886 against BPA-induced lipid accumulation in the mesenchymal-like breast cancer cell line MDA-MB-231. F1 also did not induce IL6 and CCL2 in the conditioned medium of the BPA-treated cultures. F1 is an improved, cost-effective, food-waste-derived potential PPARγ inhibitor, thereby offering a preventive strategy against early obesity caused by BPA.