Punicic acid inhibits glioblastoma migration and proliferation via the PI3K/AKT1/mTOR signaling pathway
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2019
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Abstract
Background: Punicic Acid (PA) is a polyunsaturated fatty acid that accounts for approximately 70%- 80% of Pomegranate Seed Oil (PSO). PA possesses 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 the effect of PSO on T98 glioblastoma 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. Methods: The effects of PA on cell viability; oxidative stress; and migration, proliferation, and apoptosis at the IC50 dose were studied. Results: The proliferation and migration were inhibited in the treated group compared to the non-treated group by 9.85μl/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 methods) 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 the non-treated group. Conclusion: PA 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. © 2019 Bentham Science Publishers.
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Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glioblastoma , Humans , Linolenic Acids , Molecular Structure , Oxidative Stress , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Structure-Activity Relationship , TOR Serine-Threonine Kinases , antineoplastic agent , caspase 3 , caspase 9 , endothelial nitric oxide synthase , inducible nitric oxide synthase , mammalian target of rapamycin complex 1 , matrix metalloproteinase 20 , phosphatidylinositol 3 kinase , protein kinase B , protein p53 , punicic acid , transforming growth factor beta1 , unclassified drug , vasculotropin , AKT1 protein, human , linolenic acid , MTOR protein, human , phosphatidylinositol 3 kinase , protein kinase B , punicic acid , target of rapamycin kinase , Akt signaling , angiogenesis , apoptosis , Article , cancer inhibition , cell death , cell migration , cell proliferation , cell viability , controlled study , cytotoxicity , flow cytometry , fluorescence microscopy , glioblastoma , human , human cell , IC50 , immunocytochemistry , metastasis , MTT assay , oxidative stress , scanning electron microscopy , T98 cell line , TUNEL assay , vascularization , Western blotting , wound healing assay , cell motion , cell proliferation , cell survival , chemical structure , chemistry , dose response , drug effect , drug screening , glioblastoma , metabolism , pathology , signal transduction , structure activity relation , synthesis , tumor cell line