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

Peroxisome proliferator-activated receptor (PPAR), 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 PPAR activator, extracts from five Formosan plants were tested. Among them, Momordica charantia L. showed the highest ability to activate PPAR, which led us to identify its potential constituents. Among the seven compounds isolated from M.charantia, a triterpenoid, 5,19-epoxy-19-methoxycucurbita-6,23-dien-3,25-diol (compound 1), was identified as a PPAR activator with an IC50 of 10 M 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 PPAR activation. Copyright (c) 2017 John Wiley & Sons, Ltd.