Growth inhibition of esophageal squamous carcinoma cells by peroxisome proliferator-activated receptor-gamma ligands.
The growth of human cancer cells expressing peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been reported to be inhibited by PPAR-gamma ligands. In esophageal squamous-cell carcinoma cell lines T.T, T.Tn, and EC-GI-10, we detected expression of PPAR-gamma and investigated the effects of PPAR-gamma ligands on these cell lines in vitro with the use of troglitazone, pioglitazone, and 15d-PGJ2. Marked growth inhibition by the PPAR-gamma ligands was observed in all cases. The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated with altered cell-cycle progression manifesting G1 arrest. Cell-cycle arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). Moreover, troglitazone treatment increased the expression of interleukin-1 alpha, a multifunctional cytokine implicated in antitumor immunity. These findings suggest that troglitazone and other PPAR-gamma ligands have adjuvant or neoadjuvant therapeutic potentials in esophageal cancer.
Rumi
Mohammad Azharul Karim
MA
Second Department of Internal Medicine, Shimane Medical University, Izumo, Japan. keiko@shimane-med.ac.jp
Sato
Hiroshi
H
Ishihara
Shunji
S
Ortega
Cesar
C
Kadowaki
Yasunori
Y
Kinoshita
Yoshikazu
Y
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002839:Chromans / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008024:Ligands; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
D002839:Chromans; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone