title: Peroxisome proliferator activated receptor-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells.
abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the best characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. The present study was undertaken to investigate PPAR-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase MMP-9 and MMP-2 activities on leukemia K562 and HL-60 cells in vitro. The results revealed that PPAR-gamma expression was detectable in the two kinds of leukemia cells; Both 15-deoxy-delta(12,14)-prostaglandin J2(15d-PGJ2) and troglitazone (TGZ) have significant growth inhibition effects on these two kinds of leukemia cells. These two PPAR-gamma ligands could inhibit the leukemic cell adhesion to the extracellular matrix (ECM) proteins and the invasion through matrigel matrix. The expressions of MMP-9 and MMP-2 as well as their gelatinolytic activities in both HL-60 and K562 cells were inhibited by 15d-PGJ2 and TGZ significantly. We therefore conclude that PPAR-gamma ligands 15d-PGJ2 and TGZ have significant growth inhibition effects on myeloid leukemia cells in vitro, and that PPAR-gamma ligands can inhibit K562 and HL-60 cell adhesion to and invasion through ECM as well as downregulate MMP-9 and MMP-2 expressions. The data suggest that PPAR-gamma ligands may serve as potential anti-leukemia reagents.
authors.affiliation: Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Guangzhou, 510630, P.R. China, liujj@gzsums.edu.cn.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Liu
authors.forename: Huiling
authors.initials: H
authors.lastname: Lu
authors.forename: Renwei
authors.initials: R
authors.lastname: Huang
authors.forename: Dongjun
authors.initials: D
authors.lastname: Lin
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Wu
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.forename: Xinyao
authors.initials: X
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Xianglin
authors.initials: X
authors.lastname: Pan
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Song
authors.forename: Maohong
authors.initials: M
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002839:Chromans / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology; D045726:Metalloproteases / Q000378:metabolism*; D047495:PPAR gamma / Q000494:pharmacology / Q000502:physiology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
chemical_list: C477819:15-deoxyprostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D045726:Metalloproteases; D000077288:Troglitazone; D015230:Prostaglandin D2