ArticleScientific reports2025
Targeting tumor metabolic flexibility enhances radiotherapeutic efficacy via mitochondrial complex I Inhibition in an intracranial S180 sarcoma mouse model.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Radiotherapy (RT) eliminates cancer cells by inducing DNA damage. However, its efficacy is often reduced by mechanisms such as radiation resistance, effective DNA repair, and hypoxia within tumors. Tumor cells utilize metabolic flexibility, dynamically switching between glycolysis and oxidative phosphorylation (OXPHOS) to survive and resist RT-induced stress. This study investigates how inhibiting mitochondrial complex I (CI) with IACS-010759 (IACS) enhances tumor cell sensitivity to RT, with a particular focus on metabolic disruption, DNA damage response, and overall cell survival. The potentiated effects of IACS combined with RT were evaluated in S-180 sarcoma cells using four experimental groups: control, IACS, RT, and RT + IACS. Apoptosis proteins (BAX, BCL-2, cleaved caspase-3) and radiosensitivity markers (SOD2, γH2AX) were analyzed via Western blot. ROS levels were measured by fluorescence, cell cycle by EdU-incorporated flow cytometry, p53 and p21 via Western blot, and stemness by sphere formation. In vivo, mouse intracranial tumor models underwent MRI-based tumor monitoring and survival assessment. The RT + IACS group showed heightened apoptosis via BAX/BCL-2 and caspase-3 activation, reduced SOD2, elevated ROS, and persistent γH2AX, indicating impaired DNA repair. Cell cycle analysis indicated G1/G2 phase arrest, which was associated with increased p53 and p21 expression levels, indicating p53/p21-mediated regulation, and stemness was reduced. MRI indicated the greatest tumor reduction and improved survival in the RT + IACS group. The combination of RT with metabolic inhibition effectively disrupts metabolic flexibility in S180 sarcoma, leading to ROS accumulation, impaired DNA repair, enhanced apoptosis, and reduced tumor stemness. Targeting tumor cell metabolism represents a promising strategy for enhancing RT efficacy by overcoming multiple resistance mechanisms.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.