Peroxisome proliferator-activated receptor γ agonist pioglitazone inhibits β-catenin-mediated glioma cell growth and invasion

Abstract

Gliomas are the most common primary tumors of the central nervous system. Rapid proliferation and diffuse brain invasion of these tumors are likely to determine the unfavorable prognosis. Recent studies have shown that ligand activation of peroxisome proliferator-activated receptor γ (PPARγ) can induce differentiation and inhibit proliferation of several cancer cells. In this study, we identified pioglitazone, one PPARγ ligand in particular, suppressed human glioma cells proliferation, migration, and induced glioma cells apoptosis. Concomitantly, expression level of β-catenin protein, a key molecule in carcinogenesis, was decreased in glioma cells treated with pioglitazone. Noteworthy, knockdown of β-catenin expression using siRNA technology mimicked the anti-neoplastic potency of pioglitazone. These results indicate that β-catenin is one of the mediators for pioglitazone to suppress glioma cells growth and invasion. Due to its capacity to counteract β-catenin and glioma cell proliferation and migration, pioglitazone represents a promising drug for adjuvant therapy of glioma and other highly migratory tumor entities.

Isorhamnetin Inhibits Proliferation and Invasion and Induces Apoptosis through the Modulation of Peroxisome Proliferator-activated Receptor γ Activation Pathway in Gastric Cancer

“…These have been found in all the mammalian species that have been examined to date (9,10). PPAR-␥ is highly expressed in cancer cells, and treatment with PPAR-␥ ligands can induce cell differentiation and apoptosis (11)(12)(13). Existing endogenous ligands for PPAR-␥ include polyunsaturated fatty acids and the eicosanoids 15-deoxy-⌬12,14-prostaglandin J2 (15d-PGJ2), 13-hydroxyoctadecadienoic acid, and 15-hydroxyeicosatetraenoic acid (14,15).…”

Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

“…And the cellular viability of U251 cells was reduced by 48.26% after incubation with pioglitazone 72 h at 100uM pioglitazone. The dates showed that U87 cells seemed to be more sensitive to pioglitazone than U251 cells, which was not accordant with previous finding showed that U251 cells were more sensitive than U87 cells in their response to pioglitazone [24]. And, U87 cells were used for remaining experiments.…”

“…PPARg can be activated by synthetic ligands which belonged to the thiazolidinedione (TZD) class, such as pioglitazone, troglitazone, ciglitazone [37,38]. It has been suggested that TZDs have a role of anti-glioma and can suppress the growth of glioma cells in vitro and in vivo glioma models [24,39,40]. In addition, a research conducted by Chen GL prove that pioglitazone can promote alternative splicing of REST pre-mRNA and produce a truncated protein which lose a domain essential for nuclear translocation [15].…”

15-Deoxy-Δ12,14-prostaglandin J2 inhibits migration of human thyroid carcinoma cells by disrupting focal adhesion complex and adherens junction

“…In human bladder carcinoma, 15d-PGJ 2 at a dose of 10 µM for 72 h reduced the cell survival by 90% compared with the control group (29). PPARγ agonists have been reported to block migration in several types of cancer cells (15,30). Pioglitazone, a ligand of PPARγ, suppresses human glioma cell proliferation and migration and triggers glioma cell apoptosis (15).…”

“…A previous study reported that p120-catenin (p120-ctn) regulates cell motility through the reduction of Rho GTPase activity (14). The PPARγ agonists, pioglitazone and rosiglitazone, inhibit cell growth and invasion via blocking β-catenin (β-ctn) in human glioma cells and colorectal cancer cells, respectively (15,16). The role of adherens junctions in the action of PPARγ agonists in thyroid carcinoma cells remains to be elucidated.…”