Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARγ

Deoxyelephantopin (ESD) was reported to potentiate apoptosis, inhibit invasion and abolish osteoclastogenesis but no target protein was disclosed. Here, we discovered that ESD could significantly inhibit the proliferation of different cancer cells and induce apoptosis and cell cycle arrest at G2/M phase in HeLa cell. Moreover, biochemical and biophysical assays revealed that ESD acted as a specific partial agonist against PPARγ. Molecular docking with site-directed mutagenesis analyses indicated that ESD functioned as a partial agonist of PPARγ by adopting a distinct binding mode to PPARγ compared with rosiglitazone. The PPARγ knockdown results indicated that the inhibition of ESD against the cancer cell proliferation is more possibly through PPARγ-independent pathway and our findings might supply potent binding features for ESD/PPARγ interaction at atomic level, and shed light on the potential acting target information for this natural compound.