Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARgamma.
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 G(2)/M phase in HeLa cell. Moreover, biochemical and biophysical assays revealed that ESD acted as a specific partial agonist against PPARgamma. Molecular docking with site-directed mutagenesis analyses indicated that ESD functioned as a partial agonist of PPARgamma by adopting a distinct binding mode to PPARgamma compared with rosiglitazone. The PPARgamma knockdown results indicated that the inhibition of ESD against the cancer cell proliferation is more possibly through PPARgamma-independent pathway and our findings might supply potent binding features for ESD/PPARgamma interaction at atomic level, and shed light on the potential acting target information for this natural compound.
Zou
Gang
G
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Gao
Zhenting
Z
Wang
Jidong
J
Zhang
Yu
Y
Ding
Hong
H
Huang
Jin
J
Chen
Lili
L
Guo
Yuewei
Y
Jiang
Hualiang
H
Shen
Xu
X
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D019556:COS Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007783:Lactones; D047495:PPAR gamma; D012717:Sesquiterpenes; C528427:deoxyelephantopin