New therapeutic approaches are needed to improve the outcome of patients with glioblastoma (GBM). Propionate, a short-chain fatty acid (SCFA), has a potent antiproliferative effect on various tumor cell types. Peroxisome proliferator-activated receptor (PPAR) ligands possess anticancer properties. We aimed to investigate the PPAR-γ/SCFAs interaction in in vitro and in vivo models of GBM. The U87 cell line was used in the in vitro study and was treated with sodium propionate (SP). U87 cells were silenced by using PPAR-γ siRNA or Ctr siRNA. In the in vivo study, BALB/c nude mice were inoculated in the right flank with 3 × 106 U-87 cells. SP (doses of 30 and 100 mg/kg) and GW9662 (1 mg/kg) were administered. In vitro exposure of GBM to SP resulted in prominent apoptosis activation while the autophagy pathway was promoted by SP treatments by influencing autophagy-related proteins. Knockdown of PPAR-γ sensitized GBM cells and blocked the SP effect. In vivo, SP was able to decrease tumor growth and to resolve GBM tissue features. SP promoted apoptosis and autophagy pathways and tumor cell proliferation leading to cell cycle arrest through a PPAR-γ-dependent mechanism suggesting that the PPAR-γ/SCFAs axis could be targeted for the management of GBM.
Keywords: PPAR-γ; apoptosis; autophagy; glioblastoma; short-chain fatty acids.