Peroxisome proliferator activated receptor-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells.
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.
Liu
Jiajun
J
Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Guangzhou, 510630, P.R. China, liujj@gzsums.edu.cn.
Lu
Huiling
H
Huang
Renwei
R
Lin
Dongjun
D
Wu
Xiangyuan
X
Lin
Qu
Q
Wu
Xinyao
X
Zheng
Jing
J
Pan
Xianglin
X
Peng
Jun
J
Song
Yuqin
Y
Zhang
Maohong
M
Hou
Ming
M
Chen
Feng
F
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
C477819:15-deoxyprostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D045726:Metalloproteases; D000077288:Troglitazone; D015230:Prostaglandin D2