Punicic Acid Inhibits Glioblastoma Migration and Proliferation Via the PI3K/AKT1/mTOR Signaling Pathway.

Abstract

BACKGROUND\nPunicic acid (PA) is a polyunsaturated fatty acid that accounts for approximately 70%-80% of pomegranate seed oil (PSO). PA possess strong antioxidant, anti-inflammatory, anti-atherogenic effects, and anti-tumorigenic properties. Pomegranate extracts have been shown to have anticancer activity in many studies. However, there is no evidence for effect of PSO on T98 gliobalstoma cells. Therefore, the present study was the first to investigate the mechanisms induced by PA on T98 cells, which is one of the major compounds extracted from PSO.\n\n\nMETHODS\nThe effects of PA on cell viability; oxidative stress; and migration, proliferation, and apoptosis at the IC50 dose were studied.\n\n\nRESULTS\nThe proliferation and migration were inhibited in treated group compared to non-treated group by 9,85 μl/ml PA. The difference was statistically significant (***p<0,001). Furthermore, PA induced apoptosis in the T98 glioblastoma cells compared to non-treated group and the difference was statistically significant (***p<0,001). Apoptosis was determined via immunocytochemistry staining of caspase-3, caspase-9 and TUNEL methods. Apoptosis was checked by flow cytometry (using caspase 3 method) and Scanning Electron Microscopy Analysis. We also investigated the potential signaling pathway underlying this apoptotic effect. The immunocytochemical stainings of PI3K/ Akt-1/ mTOR-1 demonstrated that, Akt-1 staining was increased with PA treatment similar to mTOR-1 and PI3K staining (***p<0,001). These increases were statistically significant compared to non-treated group.\n\n\nCONCLUSION\nPA exhibited exceptional abilities as an anticancer agent against GBM cells. The use of punicic acid in combination with other drugs used in the treatment of glioblastoma may increase the efficacy of the treatment. This study provided a basis for future investigation of its use in preclinical and clinical studies.