title: Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, independently of PPARγ in human glioma cells.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPARγ in CGZ-induced cell death was examined. At concentrations of greater than 30 μM, CGZ, a synthetic PPARγ agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 μM CGZ effectively induced cell death after pretreatment with 30 μM of the PPARγ antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPARγ was down-regulated cells by siRNA, lower concentrations of CGZ (<30 μM) were sufficient to induce cell death, although higher concentrations of CGZ (≥30 μM) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPARγ. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease in Bcl-2 expression and an increase in Bid cleavage. These data suggest that CGZ is capable of inducing apoptotic cell death independently of PPARγ in glioma cells, by down-regulating Akt activity and inducing MMP collapse.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Myoung Woo
authors.initials: MW
authors.lastname: Lee
authors.forename: Dae Seong
authors.initials: DS
authors.lastname: Kim
authors.forename: Hye Ryung
authors.initials: HR
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Somi
authors.initials: S
authors.lastname: Ryu
authors.forename: Yoo Hun
authors.initials: YH
authors.lastname: Noh
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Meong Hi
authors.initials: MH
authors.lastname: Son
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Jung
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
mesh_terms: D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D045162:Thiazolidinediones; D051057:Proto-Oncogene Proteins c-akt; C039671:ciglitazone