Peroxisome proliferator-activated receptors-gamma activator, ciglitazone, inhibits human melanocyte growth through induction of apoptosis.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. All three PPAR subtypes, PPAR-alpha, PPAR-beta/delta and PPAR-gamma are expressed in human melanocytes. In this study, we investigated the effects of PPAR-gamma activator on melanocyte growth, and apoptosis. The PPAR-gamma activators ciglitazone, troglitazone, and 15-deoxy-prostaglandin J2 inhibited melanocyte growth in a dose-dependent manner. This inhibitory effect of ciglitazone seemed to occur through induction of apoptosis. Apoptosis was increased after ciglitazone treatment, which was observed by the TUNEL method and flow cytometry. We noted a decrease in extracellular signal regulated kinase protein expression under ciglitazone treatment. Western blot analysis revealed an apparent time-dependent reduction in Bcl-2 protein levels in ciglitazone-treated melanocytes. In terms of Bax expression, a difference was not found. The expression of caspase-3 proteins was increased time-dependently with ciglitazone treatment. These results indicate that melanocyte growth and apoptosis may be modulated through PPAR-gamma and that ciglitazone, a PPAR-gamma activator, inhibits growth of human melanocytes by inducing apoptosis.
Kang
Hee Young
HY
Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea. hykang@ajou.ac.kr
Lee
Ji Yeoun
JY
Lee
Joong Sun
JS
Choi
You Mi
YM
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077288:Troglitazone; D015230:Prostaglandin D2; C039671:ciglitazone