Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with abnormal expression of genes that mediate glycolytic metabolism and tumor cell growth. Petunidin-3-O- glucoside (Pt3glc) is a kind of anthocyanin in the red grape and derived beverages, representing the most common naturally occurring anthocyanins with a reduced incidence of cancer and heart diseases. In this study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell was investigated by using the DBTRG-05MG cell lines. Notably, Pt3glc displayed potent anti-proliferative activity and significantly changed the protein levels related to both glycolytic metabolism and GBM cell survival. The expression of the pro-apoptotic protein Bax was increased with concomitant reduction on the levels of the anti-apoptotic protein Bcl-2 and caspase-3 activity. Furthermore, the levels of survival signaling proteins, such as Akt and p-Akt (Scr473), ERK and phospho-ERK, were significantly decreased by Pt3glc in combination with the PI3K inhibitor of LY294002. Most importantly, the levels of SIRT3 and phosphorylated p53 were also down-regulation, indicating that Pt3glc combinated with PI3K inhibitor could induced GBM cell death may act via the SIRT3/p53-mediated mitochondrial and PI3K/Akt-ERK pathways. Our findings thus provide rational evidence that the combination of Pt3glc with PI3K inhibitor, which target alternative pathways in GBM cells, may be a useful adjuvant therapy in glioblastoma treatment. This article is protected by copyright. All rights reserved

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