Cytotoxic flavonoids as agonists of peroxisome proliferator-activated receptor gamma on human cervical and prostate cancer cells.
We conducted in silico screening for human peroxisome proliferator-activated receptor gamma (hPPARgamma) by performing an automated docking study with 450 flavonoids. Among the eight flavonoids as possible agonists of hPPARgamma, only 3,6-dihydroxyflavone (4) increased the binding between PPARgamma and steroid receptor coactivator-1 (SRC-1), approximately 5-fold, and showed one order higher binding affinity for PPARgamma than a reference compound, indomethacin. The 6-hydroxy group of the A-ring of 3,6-dihydroxyflavone (4) participated in hydrogen-bonding interactions with the side chain of Tyr327, His449, and Tyr473. The B-ring formed a hydrophobic interaction with Leu330, Leu333, Val339, Ile341, and Met364. Therefore, 3,6-dihydroxyflavone is a potent agonist of hPPAR with cytotoxic effects on human cervical and prostate cancer cells.
Lee
Jee-Young
JY
Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Kim
Jin-Kyoung
JK
Cho
Min-Chul
MC
Shin
Soyoung
S
Yoon
Do-Young
DY
Heo
Yong Seok
YS
Kim
Yangmee
Y
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008958:Models, Molecular; D047495:PPAR gamma / Q000819:agonists*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D005419:Flavonoids; D047495:PPAR gamma