Carnosine increases efficiency of temozolomide and irradiation treatment of isocitrate dehydrogenase-wildtype glioblastoma cells in culture

Future Oncol. 2019 Nov;15(32):3683-3691. doi: 10.2217/fon-2019-0447. Epub 2019 Oct 30.

Abstract

Aim: The naturally occurring dipeptide carnosine (CAR) has been considered for glioblastoma therapy. As CAR also protects against ionizing irradiation (IR), we investigated whether it may counteract standard therapy consisting of postsurgery IR and treatment with temozolomide (TMZ). Materials & methods: Four isocitrate dehydrogenase-wildtype primary cell cultures were exposed to different doses of IR and different concentrations of TMZ and CAR. After exposure, viability under the different conditions and combinations of them was determined. Results: All cultures responded to treatment with TMZ and IR with reduced viability. CAR further decreased viability when TMZ and IR were combined. Conclusion: Treatment with CAR does not counteract glioblastoma standard therapy. As the dipeptide also protects nontumor cells from IR, it may reduce deleterious side effects of treatment.

Keywords: carnosine; glioblastoma; irradiation; radioprotection; temozolomide.

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Carnosine / pharmacology*
  • Cell Survival / drug effects*
  • Cell Survival / radiation effects
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Male
  • Middle Aged
  • Radiation, Ionizing*
  • Temozolomide / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Alkylating
  • Carnosine
  • Isocitrate Dehydrogenase
  • Temozolomide