Disease relevance of ciglitazone

• Our results demonstrated that ciglitazone and SR11237 cooperatively inhibited the growth of ZR-75-1 and T-47D breast cancer and Calu-6 lung cancer cells [1].
• Ciglitazone at 10 microM was cytoprotective for primary astrocytes but toxic to glioma cells [2].
• The PPARgamma agonist ciglitazone inhibited HIV-1 replication in a dose-dependent manner in acutely infected human MDM [3].
• We investigated the role of PPARgamma during the inflammatory response in sepsis by the use of the PPARgamma ligands, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) and ciglitazone [4].
• Treatment with 9-hydroxyoctadecanoic acids and ciglitazone significantly rescued lal-/- pulmonary inflammation and aberrant gene expression [5].
• Ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and alpha-smooth muscle actin-positive myofibroblasts [6].

High impact information on ciglitazone

• Focusing our studies on the beta/delta39 cells, we have demonstrated that C/EBPbeta along with C/EBPdelta in the presence of dexamethasone induces PPARgamma, adipsin, and aP2 mRNA production; however, GLUT4 mRNA is only expressed in cells exposed to ciglitazone [7].
• The enhanced migration of DC in the knockout mice could be blocked in vivo by anti-CCR7 antibodies and by the drug Ciglitazone, known to inhibit CCR7 expression [8].
• LNO2 activation of PPARgamma via CV-1 cell luciferase reporter gene expression analysis revealed a ligand activity that rivals or exceeds synthetic PPARgamma agonists such as rosiglitazone and ciglitazone, is coactivated by 9 cis-retinoic acid and is inhibited by the PPARgamma antagonist GW9662 [9].
• In addition, 15d-PGJ(2) but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44 expression is not affected [10].
• In PPARgamma-positive NK cells, PPAR-gamma activation by 15d-PGJ(2) and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-gamma [10].

Chemical compound and disease context of ciglitazone

• The combination of low-dose MK886, ciglitazone, and 13-cis-retinoic acid interacted at least in a superadditive fashion to inhibit the growth of lung cancer cell lines A549 and H1299, suggesting that targeting PPARgamma and AA action is a promising approach to lung cancer growth with a favorable therapeutic index [11].
• Rosiglitazone (5-20 microM) decreased survival of glioma cells without affecting primary astrocytes, whereas ciglitazone at 20 microM was toxic for both cell types [2].
• Chronic administration of ADD-3878 for as long as 12 wk to young yellow KK mice, which were in the early stage of diabetes and obesity, depressed age-dependent rises in blood glucose, plasma triglyceride, and insulin without exerting any effect on obesity [12].
• In light of the clinical relevance of targeting cyclin D1 in breast cancer, we have investigated the mechanism underlying the effect of the peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists troglitazone and ciglitazone on cyclin D1 repression [13].
• Rosiglitazone, ciglitazone, troglitazone, and PgJ (PPARgamma agonists) as well as fenofibrate (PPARalpha agonist) inhibited HIV replication in both PBMCs and U1 cells [14].

Biological context of ciglitazone

• Furthermore, we suppressed the oxidative burst by using the PPARgamma agonists 15-deoxy-Delta12,14-prostaglandin J2, BRL 49653, or ciglitazone [15].
• In this study, we used a PPARgamma dominant-negative approach and a small molecule irreversible PPARgamma antagonist and found that these inhibitors prevented PPARgamma activation but did not prevent B cell apoptosis induced by 15d-PGJ(2) or ciglitazone [16].
• Our laboratory has shown that two TZDs, ciglitazone and troglitazone, rapidly induce calcium-dependent p38 mitogen-activated protein kinase (MAPK) phosphorylation in liver epithelial cells [17].
• Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent [12].
• Peroxisome proliferator activator receptor-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J2 and ciglitazone, reduce systemic inflammation in polymicrobial sepsis by modulation of signal transduction pathways [4].

Anatomical context of ciglitazone

• MAP kinase cascades are activated in astrocytes and preadipocytes by 15-deoxy-Delta(12-14)-prostaglandin J(2) and the thiazolidinedione ciglitazone through peroxisome proliferator activator receptor gamma-independent mechanisms involving reactive oxygenated species [18].
• 15d-PGJ(2), but not ciglitazone, potently induced reactive oxygen species in B lymphocytes, implicating the reactive nature of the 15d-PGJ(2) structure in the apoptosis mechanism [16].
• Treatment of cultured 3T3-L1 adipocytes with ciglitazone increased apoE mRNA levels by 2-4-fold in a dose-dependent manner and increased apoE secretion from cells [19].
• Ciglitazone caused a dose-dependent and rapid loss (in minutes) of mitochondrial membrane potential in glioma cells [2].
• In addition, treatment of human monocyte-derived macrophages with ciglitazone did not regulate expression of apoE [19].

Associations of ciglitazone with other chemical compounds

• In reporter gene assays, RXR ligands and ciglitazone, but not the PPAR gamma ligand 15d-PGJ(2), cooperatively promoted the transcriptional activity of the beta retinoic acid response element [1].
• PPARgamma ligands, including the endogenous ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) and synthetic ligands like ciglitazone and troglitazone, all induce apoptosis in normal and malignant human B lymphocytes, but the dependency of PPARgamma for apoptosis induction is unknown [16].
• Another thiazolidinedione that binds to PPAR gamma, rosiglitazone, does not activate MAP kinases, indicating that the effect of ciglitazone on MAP kinases is independent of PPAR gamma [18].
• Ciglitazone (20 microm), a thiazolidinedione that mimics several effects of dPGJ2 in different cell types, also activates the three MAP kinase families and ASK1 in cultured astrocytes [18].
• The data showed that ciglitazone increased the basal rate of glucose metabolism, lipogenesis, insulin receptor number, and post-receptor responses in the C57BL/6J-ob/ob mice; it increased the basal rate of glucose metabolism and lipogenesis but not insulin sensitivity in the lean mice [20].

Gene context of ciglitazone

• In this study, we have examined the effects of the PPAR gamma ligand ciglitazone and the RXR ligand SR11237 on growth and induction of retinoic acid receptor (RAR) beta expression in breast and lung cancer cells [1].
• Ciglitazone, but not 15d-PGJ(2), strongly induced RAR beta expression in human breast and lung cancer cell lines when used together with SR11237 [1].
• In the current study, we demonstrate that various PPARalpha (nafenopin) and gamma (ciglitazone and troglitazone) agonists rapidly induced extracellular signal-regulated kinase (Erk) and/or p38 phosphorylation in rat liver epithelial cells (GN4) [21].
• The results show that IFN-gamma-induced inducible NO synthase (iNOS) gene transcription, iNOS protein induction, and NO production are more sensitive to inhibition by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) than by the other two PPARgamma agonists, GW1929 and ciglitazone [22].
• In murine C2C12 myoblasts, treatment with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), ciglitazone, and GW1929 leads to ERK1/2 phosphorylation in a time- and concentration-dependent manner [23].

Analytical, diagnostic and therapeutic context of ciglitazone

• Ciglitazone, 5-[4-(1-methylcyclohexylmethoxy) benzyl]-thiazolidine-2,4-dione, is a new hypoglycemic agent orally active in the obese-hyperglycemic animal models [24].
• Ciglitazone also suppressed HIV-1 mRNA levels as measured by reverse transcriptase PCR, in parallel with the decrease in reverse transcriptase activity [3].
• Interestingly, only Thy-1(-), but not Thy-1(+) subsets differentiated to lipofibroblasts, as determined by the accumulation of cytoplasmic lipid droplets after treatment with 15-deoxy-Delta(12, 14)-PGJ(2) or ciglitazone [25].
• Oral administration of ciglitazone, approximately 45 mg/kg per day for 4 weeks, induced significant reductions in plasma insulin levels (p < 0.001) and blood pressure (p < 0.05) [26].
• Using ciglitazone as the model compound, the mechanism of the antiproliferative effect of PPARgamma activators on MAPK and specific cell cycle regulatory proteins were examined by Western blot analysis and transfection studies [27].

References