The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro

Int J Mol Sci. 2022 Sep 9;23(18):10455. doi: 10.3390/ijms231810455.

Abstract

In this study, pyruvate dehydrogenase kinase-1 inhibition with dichloroacetate (DCA) was explored as an alternative cancer therapy. The study's aim was to compare the effectiveness of NaDCA and MgDCA on pediatric glioblastoma PBT24 and SF8628 tumors and cells. The treatment effects were evaluated on xenografts growth on a chicken embryo chorioallantoic membrane. The PCNA, EZH2, p53, survivin expression in tumor, and the SLC12A2, SLC12A5, SLC5A8, CDH1, and CDH2 expression in cells were studied. The tumor groups were: control, cells treated with 10 mM and 5 mM of NaDCA, and 5 mM and 2.5 mM of MgDCA. The cells were also treated with 3 mM DCA. Both the 10 mM DCA preparations significantly reduced PBT24 and SF8624 tumor invasion rates, while 5 mM NaDCA reduced it only in the SF8628 tumors. The 5 mM MgDCA inhibited tumor-associated neoangiogenesis in PBT24; both doses of NaDCA inhibited tumor-associated neoangiogenesis in SF8628. The 10 mM DCA inhibited the expression of markers tested in PBT24 and SF8628 tumors, but the 5 mM DCA affect on their expression depended on the cation. The DCA treatment did not affect the SLC12A2, SLC12A5, and SLC5A8 expression in cells but increased CDH1 expression in SF8628. The tumor response to DCA at different doses indicated that a contrast between NaDCA and MgDCA effectiveness reflects the differences in the tested cells' biologies.

Keywords: CAM model; PBT24; SF8628; dichloroacetate; gene expression; pediatric glioblastoma; sex.

MeSH terms

  • Acetates / therapeutic use
  • Animals
  • Chick Embryo
  • Chickens / metabolism
  • Chorioallantoic Membrane / metabolism
  • Dichloroacetic Acid / pharmacology
  • Glioblastoma* / metabolism
  • Humans
  • Magnesium / metabolism
  • Monocarboxylic Acid Transporters
  • Proliferating Cell Nuclear Antigen / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Sodium / metabolism
  • Solute Carrier Family 12, Member 2
  • Survivin / metabolism
  • Tumor Suppressor Protein p53

Substances

  • Acetates
  • Monocarboxylic Acid Transporters
  • Proliferating Cell Nuclear Antigen
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • SLC12A2 protein, human
  • SLC5A8 protein, human
  • Solute Carrier Family 12, Member 2
  • Survivin
  • Tumor Suppressor Protein p53
  • Dichloroacetic Acid
  • Sodium
  • Magnesium