The Ligands of Peroxisome Proliferator-activated Receptor (PPAR) Gamma Inhibit Growth of Human Esophageal Carcinoma Cells through Induction of Apoptosis and Cell Cycle Arrest

• Published in: Anticancer research 2004-05, Vol.24 (3A), p.1409-1416
• Main Authors: FUJII, Daisuke, YOSHIDA, Kazuhiro, TANABE, Kazuaki, HIHARA, Jun, TOGE, Tetsuya
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Blotting, Western; Cell Cycle - drug effects; Cell Cycle Proteins - biosynthesis; Cell Division - drug effects; Cell Line, Tumor; Chromans - pharmacology; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophagus; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic - drug effects; Humans; Ligands; Medical sciences; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - metabolism; Thiazolidinediones - pharmacology; Transcription Factors - biosynthesis; Transcription Factors - metabolism; Tumors
• ISSN: 0250-7005; 1791-7530

In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and the growth-inhibitory effects of Troglitazone and Pioglitazone, selective ligands for PPARγ, using a series of human esophageal carcinoma cell lines (TE-1, -3, -7, -8, -12 and -13). PPARγ 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 G 1 -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 G 1 arrest and apoptosis and that PPARγ ligands should be considered as possible target molecules in the treatment of human esophageal carcinomas.