Effects of Disulfiram and Copper in Combination with Temozolomide on Survival, Tumor Size and Autophagy Markers in an F98 Rat Glioma Model
Year: 2026
Type: article
Abstract: Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults with a median survival of 15 months. One of the main factors responsible for the poor prognosis of GBM is resistance to treatment with temozolomide (TMZ), which has been attributed-among other factors-to autophagy. Preclinical studies have shown that the combination of disulfiram (DSF) with copper (Cu) possesses anti-GBM activity, through various mechanisms, including re-sensitization to TMZ. Herein, we tested for the first time the effects of DSF and Cu in combination with TMZ on the survival of Fischer rats bearing F98 glioma, a model characterized by inherent resistance to TMZ. Tumor size evaluation by Magnetic Resonance Imaging as well as immunofluorescence analysis of two autophagy markers, namely microtubule-associated protein 1 light chain 3 (LC3) and sequestosome-1 (SQSTM1)/p62 (p62), were also performed. According to our results, TMZ-DSF-Cu significantly increased mean survival and induced both LC3 and p62 autophagy markers. Interestingly, these results could not be achieved in the absence of Cu, neither in the presence of TMZ alone, suggesting the importance of combining DSF with Cu in order to sensitize glioma to TMZ, presumably via implication of autophagy modulation.
DOI: 10.3390/ijms27041966
Institutions: University of Ioannina, Patras Olympian Hospital, Academy of Athens, Biomedical Research Foundation of the Academy of Athens, University of Patras, National Centre of Scientific Research "Demokritos", Institute of Biosciences & Applications, National and Kapodistrian University of Athens, 401 General Military Hospital of Athens, European University Cyprus, Aretaeio Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7130346456