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Article

Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells

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Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4 Święcicki Str., 60-781 Poznań, Poland
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Department of Pharmacognosy, Poznan University of Medical Sciences, 4 Święcicki Str., 60-781 Poznań, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Beatrice E. Bachmeier and Peter Hau
Int. J. Mol. Sci. 2021, 22(20), 11285; https://doi.org/10.3390/ijms222011285
Received: 24 September 2021 / Revised: 13 October 2021 / Accepted: 18 October 2021 / Published: 19 October 2021
(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)
Glioblastoma (GBM) is an extremely aggressive brain tumor awaiting novel, efficient, and minimally toxic treatment. Curcuminoids (CCM), polyphenols from Curcuma longa, and sodium butyrate (NaBu), a histone deacetylase inhibitor naturally occurring in the human body, await elucidation as potential anti-GBM agents. Thus, the aim of this study was to analyze CCM and NaBu both separately and as a combination treatment using three GBM cell lines. MTT was used for cytotoxicity evaluation, and the combination index was calculated for synergism prediction. Cell cycle, apoptosis, and reactive oxygen species (ROS) generation were analyzed using flow cytometry. DNA methylation was verified by MS-HRM and mRNA expression by qPCR. The permeability through the blood-brain barrier (BBB) and through the nasal cavity was evaluated using PAMPA model. The results of this study indicate that CCM and NaBu synergistically reduce the viability of GBM cells inducing apoptosis and cell cycle arrest. These effects are mediated via ROS generation and changes in gene expression, including upregulation of Wnt/β-catenin pathway antagonists, SFRP1, and RUNX3, and downregulation of UHRF1, the key epigenetic regulator. Moreover, NaBu ameliorated CCM permeability through the BBB and the nasal cavity. We conclude that CCM and NaBu are promising agents with anti-GBM properties. View Full-Text
Keywords: curcuminoids; sodium butyrate; glioblastoma; cell cycle; apoptosis; reactive oxygen species; DNA methylation; permeability curcuminoids; sodium butyrate; glioblastoma; cell cycle; apoptosis; reactive oxygen species; DNA methylation; permeability
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MDPI and ACS Style

Majchrzak-Celińska, A.; Kleszcz, R.; Stasiłowicz-Krzemień, A.; Cielecka-Piontek, J. Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells. Int. J. Mol. Sci. 2021, 22, 11285. https://doi.org/10.3390/ijms222011285

AMA Style

Majchrzak-Celińska A, Kleszcz R, Stasiłowicz-Krzemień A, Cielecka-Piontek J. Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells. International Journal of Molecular Sciences. 2021; 22(20):11285. https://doi.org/10.3390/ijms222011285

Chicago/Turabian Style

Majchrzak-Celińska, Aleksandra, Robert Kleszcz, Anna Stasiłowicz-Krzemień, and Judyta Cielecka-Piontek. 2021. "Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells" International Journal of Molecular Sciences 22, no. 20: 11285. https://doi.org/10.3390/ijms222011285

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