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

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.

Nobiletin inhibits viability of human renal carcinoma cells via the JAK2/STAT3 and PI3K/Akt pathway

“…In addition to inhibiting the proliferation of tumor cells, this study also demonstrated that nobiletin inhibited the migration and invasion of renal cancer cells. Earlier studies have shown that inhibition of Akt expression suppressed cell migration (23)(24).The results of this study indicate that nobiletin inhibited the activation of Akt, which may be one of the mechanisms by which nobiletin inhibited the invasion and migration of renal cancer cells.…”

Nobiletin Inhibits Cell Viability via the SRC/AKT/STAT3/YY1AP1 Pathway in Human Renal Carcinoma Cells

“…Notably, this was also observed for the highly invasive ACHN cells, which are derived from pleural effusion metastasis. Earlier studies have shown that activating AKT inhibition can suppress cell migration (Marcial-Medina et al, 2019; Mete et al, 2019). Our own results indicated that nobiletin inhibits AKT activation, suggesting that this could be one of the mechanisms underlying the inhibitory effect of nobiletin on the invasion and migration of renal carcinoma cells.…”

Metagenomic and Metabolomic Analyses Reveal Synergistic Effects of Fecal Microbiota Transplantation and Anti-PD-1 Therapy on Treating Colorectal Cancer

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