The ligands of peroxisome proliferator-activated receptor (PPAR) gamma inhibit growth of human esophageal carcinoma cells through induction of apoptosis and cell cycle arrest.
In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the growth-inhibitory effects of Troglitazone and Pioglitazone, selective ligands for PPARgamma, using a series of human esophageal carcinoma cell lines (TE-1, -3, -7, -8, -12 and -13). PPARgamma expression was detected in all six human esophageal carcinoma cell lines. The esophageal carcinoma cell line TE-13 showed marked growth inhibition in response to Troglitazone and Pioglitazone. Flow cytometry performed on TE-13 cells exposed to Troglitazone showed that the cell cycle was arrested at the G1-phase. This result was confirmed by the finding of reduced cyclin D and cyclin E expression by Western blot analysis. DNA ladder formation was also detected, as was the induction of apoptosis-related proteins. Our results suggested that Troglitazone inhibited the growth of human esophageal carcinoma cell lines via G1 arrest and apoptosis and that PPARgamma ligands should be considered as possible target molecules in the treatment of human esophageal carcinomas.
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. dai9318@hiroshima-u.ac.jp
Daisuke
D
Fujii
Kazuhiro
K
Yoshida
Kazuaki
K
Tanabe
Jun
J
Hihara
Tetsuya
T
Toge
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008024:Ligands; D000077205:Pioglitazone; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D000077288:Troglitazone
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002839:Chromans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D000077205:Pioglitazone