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. 2024 Jun 25;12(7):1416.
doi: 10.3390/biomedicines12071416.

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Affiliations

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Milda Juknevičienė et al. Biomedicines. .

Abstract

Valproic acid (VPA) has anticancer, anti-inflammatory, and epigenetic effects. The study aimed to determine the expression of carcinogenesis-related SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 in adult glioblastoma U87 MG and T98G cells and the effects of 0.5 mM, 0.75 mM, and 1.5 mM doses of VPA. RNA gene expression was determined by RT-PCR. GAPDH was used as a control. U87 and T98G control cells do not express SLC5A8 or CDH1. SLC12A5 was expressed in U87 control but not in T98G control cells. The SLC12A2 expression in the U87 control was significantly lower than in the T98G control. T98G control cells showed significantly higher CDH2 expression than U87 control cells. VPA treatment did not affect SLC12A2 expression in U87 cells, whereas treatment dose-dependently increased SLC12A2 expression in T98G cells. Treatment with 1.5 mM VPA induced SLC5A8 expression in U87 cells, while treatment of T98G cells with VPA did not affect SLC5A8 expression. Treatment of U87 cells with VPA significantly increased SLC12A5 expression. VPA increases CDH1 expression depending on the VPA dose. CDH2 expression was significantly increased only in the U87 1.5 mM VPA group. Tested VPA doses significantly increased CDH2 expression in T98G cells. When approaching treatment tactics, assessing the cell's sensitivity to the agent is essential.

Keywords: CDH1; CDH2; KCC2; NKCC1; SLC5A8; T98G cell; U87 MG cell; adult glioblastoma; valproic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

References

    1. D’Amico R.S., Englander Z.K., Canoll P., Bruce J.N. Extent of Resection in Glioma-A Review of the Cutting Edge. World Neurosurg. 2017;103:538–549. doi: 10.1016/j.wneu.2017.04.041. - DOI - PubMed
    1. Thotala D., Karvas R.M., Engelbach J.A., Garbow J.R., Hallahan A.N., DeWees T.A., Laszlo A., Hallahan D.E. Valproic Acid Enhances the Efficacy of Radiation Therapy by Protecting Normal Hippocampal Neurons and Sensitizing Malignant Glioblastoma Cells. Oncotarget. 2015;6:35004–35022. doi: 10.18632/oncotarget.5253. - DOI - PMC - PubMed
    1. Chang C.Y., Li J.R., Wu C.C., Ou Y.C., Chen W.Y., Kuan Y.H., Wang W.Y., Chen C.J. Valproic Acid Sensitizes Human Glioma Cells to Gefitinib-Induced Autophagy. IUBMB Life. 2015;67:869–879. doi: 10.1002/iub.1445. - DOI - PubMed
    1. Lu V.M., Texakalidis P., McDonald K.L., Mekary R.A., Smith T.R. The Survival Effect of Valproic Acid in Glioblastoma and Its Current Trend: A Systematic Review and Meta-Analysis. Clin. Neurol. Neurosurg. 2018;174:149–155. doi: 10.1016/j.clineuro.2018.09.019. - DOI - PubMed
    1. Kresbach C., Bronsema A., Guerreiro H., Rutkowski S., Schüller U., Winkler B. Long-Term Survival of an Adolescent Glioblastoma Patient under Treatment with Vinblastine and Valproic Acid Illustrates Importance of Methylation Profiling. Childs Nerv. Syst. 2022;38:479–483. doi: 10.1007/s00381-021-05278-6. - DOI - PMC - PubMed

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