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Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds

Int J Mol Sci. 2022 May 23;23(10):5834. doi: 10.3390/ijms23105834.

Abstract

The naturally occurring dipeptide carnosine (β-alanyl-L-histidine) specifically attenuates tumor growth. Here, we ask whether other small imidazole-containing compounds also affect the viability of tumor cells without affecting non-malignant cells and whether the formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L-alanyl-L-histidine (LA-LH), β-alanyl-L-alanine, L-histidine, histamine, imidazole, β-alanine, and L-alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L-histidine and formation of histamine was investigated by high-performance liquid chromatography coupled to mass spectrometry. Carnosine and LA-LH inhibited tumor cell growth with minor effects on fibroblasts, and L-histidine, histamine, and imidazole affected viability in both cell types. Compounds without the imidazole moiety did not diminish viability. In the presence of LA-LH but not in the presence of carnosine, a significant rise in intracellular amounts of histidine was detected in all cells. The formation of histamine was not detectable in the presence of carnosine, LA-LH, or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA-LH. Despite the fact that histamine has a strong effect on cell viability, the formation of histamine is not responsible for the effects on the cell viability of carnosine, LA-LH, and histidine.

Keywords: carnosine; cell viability; fibroblasts; glioblastoma; high-performance liquid chromatography coupled to mass spectrometry; imidazole-containing compounds.

MeSH terms

  • Alanine
  • Carnosine* / metabolism
  • Fibroblasts / metabolism
  • Glioblastoma* / drug therapy
  • Glioblastoma* / metabolism
  • Histamine / metabolism
  • Histamine / pharmacology
  • Histidine / metabolism
  • Humans
  • Imidazoles / pharmacology
  • beta-Alanine

Substances

  • Imidazoles
  • beta-Alanine
  • Histidine
  • Histamine
  • Carnosine
  • Alanine

Grants and funding

Funded by the Open Access Publishing Fund of Leipzig University supported by the German Research Foundation within the program Open Access Publication Funding.