Cystathionine Promotes the Proliferation of Human Astrocytoma U373 Cells

Anticancer Res. 2018 Jun;38(6):3501-3505. doi: 10.21873/anticanres.12621.

Abstract

Background/aim: In certain cancers, accumulation of cystathionine has been observed. The present study investigated the effect of cystathionine on astrocytoma (U373) cell proliferation, the activity of γ-cystathionase (CTH) and changes in thiols levels.

Materials and methods: The methods used in the study included cytotoxicity assay, crystal violet staining method, CTH activity assay and reverse phase-high performance liquid chromatography (RP-HPLC).

Results: The addition of cystathionine to the culture medium resulted in an increase of cystathionine level in U373 cells after 24 h of culture. Reduction of intracellular cystathionine level after 48 and 72 h of culture was associated with increased L-cysteine and L-cystine levels and stimulation of cell proliferation. Interestingly, a decrease in intracellular L-cysteine and L-cystine levels during the first hours of culture was observed.

Conclusion: Elevated levels of cystathionine resulted in increased U373 cell proliferation by increasing the L-cysteine levels and GSH/GSSG ratio (especially after 72 h of the culture), but not with a simultaneous increase in the levels of total glutathione.

Keywords: Cystathionine; brain cancer cells; hydrogen sulfide; sulfurtransferases; thiols.

MeSH terms

  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cystathionine / metabolism*
  • Cystathionine / pharmacology*
  • Cystathionine gamma-Lyase / metabolism
  • Cysteine / metabolism
  • Cystine / metabolism
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Time Factors

Substances

  • Cystathionine
  • Cystine
  • Cystathionine gamma-Lyase
  • Glutathione
  • Cysteine
  • Glutathione Disulfide