title: Cytotoxicity of troglitazone through PPARγ-independent pathway and p38 MAPK pathway in renal cell carcinoma.
abstract: Agonists of peroxisome proliferator-activated receptor gamma (PPARγ) have been examined as chemopreventive and chemotherapeutic agents. The aim was to investigate the cytotoxicity of troglitazone (TGZ) and its mechanisms in terms of PPARγ dependency and the p38 mitogen-activated protein kinase (MAPK) pathway in three human renal cell carcinoma (RCC) cell lines, 786-O, Caki-2 and ACHN cells. TGZ induced apoptosis and exerted cytotoxicity in a PPARγ-independent manner. We demonstrated that TGZ activated the p38 MAPK pathway and was involved in the cytotoxicity of TGZ. It was also revealed that TGZ induced G(2)/M cell cycle arrest through activation of p38 MAPK.
authors: Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors: Megumi
authors: M
authors: Fujita
authors: Tatsurou
authors: T
authors: Yagami
authors: Miki
authors: M
authors: Fujio
authors: Chiaki
authors: C
authors: Tohji
authors: Kenkichi
authors: K
authors: Takase
authors: Yasuhiro
authors: Y
authors: Yamamoto
authors: Kyoko
authors: K
authors: Sawada
authors: Motohiro
authors: M
authors: Yamamori
authors: Noboru
authors: N
authors: Okamura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; D000077288:Troglitazone