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Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Aug 30; Vol. 25 (17). Date of Electronic Publication: 2024 Aug 30. - Publication Year :
- 2024
-
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 m <superscript>5</superscript> CpG 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.
- Subjects :
- Humans
Cell Line, Tumor
Brain Neoplasms drug therapy
Brain Neoplasms metabolism
Oxidative Stress drug effects
Epigenesis, Genetic drug effects
5-Methylcytosine metabolism
5-Methylcytosine analogs & derivatives
Metformin pharmacology
Metformin therapeutic use
Glioblastoma drug therapy
Glioblastoma metabolism
Arginine metabolism
Drug Repositioning methods
DNA Methylation drug effects
Temozolomide therapeutic use
Temozolomide pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39273414
- Full Text :
- https://doi.org/10.3390/ijms25179460