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Original Paper

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Valproic Acid Promotes Human Glioma U87 Cells Apoptosis and Inhibits Glycogen Synthase Kinase-3β Through ERK/Akt Signaling

Zhang C.a · Liu S.a · Yuan X.a · Hu Z.b · Li H.a · Wu M.a · Yuan J.a · Zhao Z.a · Su J.a · Wang X.a · Liao Y.a · Liu Q.a

Author affiliations

aDepartment of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan, bDepartment of Pathology, Xiangya Hospital, Central-South University, Changsha, Hunan, China

Corresponding Author

Qing Liu

Department of Neurosurgery, Xiangya Hospital,

Central-South University, Changsha, Hunan, 410008 (China)

E-Mail liuqcsu@hotmail.com

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Cell Physiol Biochem 2016;39:2173-2185

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Abstract

Background: Valproic acid (VPA), an established antiepileptic drug, was assessed for antitumor activity, including its effects on glioblastoma, but its role has not been determined. Methods: In the present study, we investigated VPA-induced apoptosis effects on human U87 cells by cell viability, lactate dehydrogenase (LDH) release, TUNEL/Hoechst staining and flow cytometric in vitro, then we further explored the underlying molecular mechanisms using the selective antagonists PD98059, LY294002 and SB216763. Results: The data showed that VPA dose-dependent induction of glioma U87 cells to undergo apoptosis through the mitochondria-dependent pathway in vitro. VPA activated the ERK/Akt pathways by increasing their protein phosphorylation and in turn inhibited GKS3β activation by the induction of GKS3β phosphorylation. However, the MAPK inhibitor PD98059 and/or PI3K inhibitor LY294002 were able to antagonize the effects of VPA by abolishing ERK/Akt activations and cancelling GSK3β suppression, thus it impaired VPA apoptosis-inducing effects on glioma cells. Furthermore, the GSK3β inhibitor SB216763 caused a strong suppression of GSK3β activity, which showed similar effects of VPA on regulation of protein expression and apoptosis. Conclusion: These findings suggest that GSK3β may be the central hub for VPA-induced apoptosis and VPA can be further evaluated as a novel agent for glioma therapy.

© 2016 The Author(s) Published by S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: September 08, 2016
Published online: November 02, 2016
Issue release date: November 2016

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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