title: Cytotoxic flavonoids as agonists of peroxisome proliferator-activated receptor gamma on human cervical and prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Cho
authors.forename: Soyoung
authors.initials: S
authors.lastname: Shin
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D047495:PPAR gamma