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Quercetin and Sodium Butyrate Synergistically Increase Apoptosis in Rat C6 and Human T98G Glioblastoma Cells Through Inhibition of Autophagy

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Abstract

This study investigated the efficacy of quercetin (QCT) in combination with sodium butyrate (NaB) in enhancing apoptosis in rat C6 and human T98G glioblastoma cells though blockage of autophagy under nutrient-starvation. The most synergistic doses of the drugs were determined to be 25 µM QCT and 1 mM NaB in both cell lines. After QCT and QCT + NaB treatments, autophagy quantification with acridine orange staining showed a drastic decrease in protective autophagy in the cells under nutrient-starvation. Decrease in autophagy was correlated with decreases in expression of Beclin-1 and LC3B II. Combination treatment increased the morphological signs of apoptosis including membrane blebbing, nuclear fragmentation, and chromatin condensation. Annexin V staining was also performed for detection and quantification of increases in apoptosis. Western blotting results showed that combination of QCT and NaB increased apoptosis by decreasing anti-apoptotic Bcl-2 and increasing pro-apoptotic Bax, decreasing survivin, activating caspase-3, and degrading poly (ADP-ribose) polymerase (PARP). This study demonstrated the therapeutic potentials of a novel combination therapy in inhibiting protective autophagy to enhance apoptosis in rat C6 and human T98G glioblastoma cells.

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Acknowledgements

This work was supported in part by an award from the Soy Health Research Program (SHRP, United Soybean Board, Chesterfield, MO, USA), a Grant (SCIRF-2015-I-0) from the Spinal Cord Injury Research Fund (SCIRF, Columbia, SC, USA), and also earlier R01 Grants (CA91460 and NS57811) from the National Institutes of Health (Bethesda, MD, USA).

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  1. Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC, 29209, USA

    Matthew A. Taylor, Firas Khathayer & Swapan K. Ray

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  1. Matthew A. Taylor
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Correspondence to Swapan K. Ray.

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Taylor, M.A., Khathayer, F. & Ray, S.K. Quercetin and Sodium Butyrate Synergistically Increase Apoptosis in Rat C6 and Human T98G Glioblastoma Cells Through Inhibition of Autophagy. Neurochem Res 44, 1715–1725 (2019). https://doi.org/10.1007/s11064-019-02802-8

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  • DOI: https://doi.org/10.1007/s11064-019-02802-8

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