Ligands for the peroxisome proliferator-activated receptor-gamma have inhibitory effects on growth of human neuroblastoma cells in vitro.
The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-gamma (PPAR-gamma) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-gamma agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-gamma protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 microM and 100 microM). Effectiveness of the glitazones on neuroblastoma cell growth differed depending on the cell line and the agent. The presence of PPAR-gamma protein was demonstrated in all cell lines. Our findings indicate that ligands for PPAR-gamma may be useful therapeutic agents for the treatment of neuroblastoma. Thus the effect of glitazones on the growth of neuroblastoma should now be investigated in an in vivo animal model.
Valentiner
Ursula
U
Institute for Anatomy II: Experimental Morphology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany. valentin@uke.uni-hamburg.de
Carlsson
Margarita
M
Erttmann
Rudolf
R
Hildebrandt
Herbert
H
Schumacher
Udo
U
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008024:Ligands; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005562:Formazans; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan