Differential curcumin absorption and curcumin-induced STAT3 inhibition during 3T3-L1 cell adipogenesis in 2D and 3D cultures

Abstract

AbstractIt is increasingly considered that 3D cell culture systems are superior to 2D in evaluating health promoting effects of candidate molecules because they better mimic tissue-like structures, thus testing in such systems will increase their in vivo applicability. The present study sought to examine the potential usefulness of spheroid models for assessing the antiadipogenic effect of polyphenols. The major food polyphenols were compared for their antiadipogenic effects in 3T3-L1 cells grown in conventional 2D conditions and as 3D spheroids. Further, the study evaluated the effect of the cell culture environment on the inhibition of the adipogenesis-related signaling pathway mediated by curcumin (CUR), the most effective antiadipogenic polyphenol identified in 2D and 3D, and its cellular absorption rate. CUR treatment inhibited the activity of signal transducer and activator of transcription 3 (STAT3) in cells cultured in both conditions; however, it was more effective in 2D. Notably, 3T3-L1 preadipocytes in a 3D cell culture system maintained high STAT3 activity and CCAAT/enhancer-binding protein alpha (C/EBPα) expression compared with a 2D system. Additionally, the cellular absorption rate was lower in 3D cultures. Thus, different cellular absorption rates, innate STAT3 activity, and C/EBPα expression levels may contribute to the difference in CUR efficacy. This study demonstrated that the STAT3 inhibition at least partly contributes to antiadipogenic effect of CUR. Moreover, it showed that the presentation of cells in 3D significantly alters activation of intracellular signaling pathways and absorption rate of CUR. Therefore, 3D spheroid models are valuable tools to evaluate the anti-adipogenicity of candidate molecules.