Open Access
Open access
International Journal of Molecular Sciences, volume 25, issue 17, pages 9460

Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment

Anna-Maria Barciszewska 1, 2
Agnieszka Belter 3
Jakub F. Barciszewski 3
Iwona Gawrońska 3
Małgorzata Giel-Pietraszuk 3
Mirosława Z. Naskręt-Barciszewska 3
1
 
Intraoperative Imaging Unit, Chair and Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland
2
 
Department of Neurosurgery and Neurotraumatology, University Clinical Hospital, Przybyszewskiego 49, 60-355 Poznan, Poland
Publication typeJournal Article
Publication date2024-08-30
scimago Q1
SJR1.179
CiteScore8.1
Impact factor4.9
ISSN16616596, 14220067
Abstract

As the most common and aggressive primary malignant brain tumor, glioblastoma is still lacking a satisfactory curative approach. The standard management consisting of gross total resection followed by radiotherapy and chemotherapy with temozolomide only prolongs patients’ life moderately. In recent years, many therapeutics have failed to give a breakthrough in GBM treatment. In the search for new treatment solutions, we became interested in the repurposing of existing medicines, which have established safety profiles. We focused on the possible implementation of well-known drugs, metformin, and arginine. Metformin is widely used in diabetes treatment, but arginine is mainly a cardiovascular protective drug. We evaluated the effects of metformin and arginine on total DNA methylation, as well as the oxidative stress evoked by treatment with those agents. In glioblastoma cell lines, a decrease in 5-methylcytosine contents was observed with increasing drug concentration. When combined with temozolomide, both guanidines parallelly increased DNA methylation and decreased 8-oxo-deoxyguanosine contents. These effects can be explained by specific interactions of the guanidine group with m5CpG dinucleotide. We showed that metformin and arginine act on the epigenetic level, influencing the foreground and potent DNA regulatory mechanisms. Therefore, they can be used separately or in combination with temozolomide, in various stages of disease, depending on desired treatment effects.

Top-30

Journals

1
1

Publishers

1
1
  • We do not take into account publications without a DOI.
  • Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
  • Statistics recalculated weekly.

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.
Share
Cite this
GOST | RIS | BibTex | MLA
Found error?