Identification of a Triterpenoid as a Novel PPARγ Activator Derived from Formosan Plants

Peroxisome proliferator-activated receptor γ (PPARγ), one of the transcription factors that regulate lipid metabolism and energy use in tumor cells, is a viable target for cancer therapy. In our search for potential PPARγ activator, extracts from five Formosan plants were tested. Among them, Momordica charantia L. showed the highest ability to activate PPARγ, which led us to identify its potential constituents. Among the seven compounds isolated from M. charantia, a triterpenoid, 5β,19-epoxy-19-methoxycucurbita-6,23-dien-3β,25-diol (compound 1), was identified as a PPARγ activator with an IC₅₀ of 10 μM in breast cancer MCF-7 cells. Flow cytometric analysis indicated that compound 1 induced G1 cell cycle arrest which might be attributable to the modulation of phosphorylation and expression of numerous key signaling effectors, including cyclin D1, CDK6, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 1, leading to increased histone H3 acetylation. Taken together, these findings suggest that compound 1 may have therapeutic applications in cancer treatment through PPARγ activation. Copyright © 2017 John Wiley & Sons, Ltd.