MAT2a and AHCY Inhibition Disrupts Antioxidant Metabolism and Reduces Glioblastoma Cell Survival DOI Creative Commons
Emma Rowland, Matthew D’Antuono,

Anna Jermakowicz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 24, 2024

Abstract Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with fatal prognosis. This due in part to metabolic reprogramming allows tumors evade treatment. We therefore must uncover the pathways mediating these adaptations develop novel and effective treatments. searched for genes are essential GBM cells as measured by whole-genome pan-cancer CRISPR screen available from DepMap identified methionine metabolism MAT2A AHCY . conducted genetic knockdown, evaluated mitochondrial respiration, performed targeted metabolomics study function of GBM. demonstrate or knockdown induces oxidative stress, hinders cellular reduces survival cells. Furthermore, selective MAT2a inhibition cell viability, impairs metabolism, changes profile towards stress death. Mechanistically, regulates spare respiratory capacity, redox buffer cystathionine, lipid amino acid prevents DNA damage Our results point pathway vulnerability Significance demonstrated maintains antioxidant production facilitate pro-tumorigenic ROS signaling survival. Importantly, targeting this can potentially reduce growth improve patients.

Language: Английский

Application of Nanomaterial-Mediated Ferroptosis Regulation in Kidney Disease DOI Creative Commons
Jiamin Zhu, Zhen Zhang,

Yanhui Chu

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 1637 - 1659

Published: Feb. 1, 2025

Abstract: Kidney diseases are a significant global cause of death and disability, resulting from the destruction kidney structure function due to an imbalance between renal parenchymal cells proliferation or recruitment maladaptive cells, caused by various pathogenic factors. Currently, therapies their efficacy for limited. Ferroptosis is newly discovered iron-dependent regulated cell death. The iron homeostasis lipid metabolism affects occurrence progression triggering ferroptosis, which considered important target development disease drugs. However, in clinical practice, targeted ferroptosis therapy faces obstacles such as poor drug solubility, low resistance, imprecise targeting. With rapid nanomaterials medical field, new opportunities have emerged precise regulation treatment diseases. This article provides detailed introduction regulatory mechanisms properties nanomaterials, application diseases, with focus on discussing action therapeutic potential based aim this provide ideas directions future treatments. Keywords: nanomaterial, nanomedicine,

Language: Английский

Citations

0
Methionine cycle inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival DOI Creative Commons

Elizabeth A. Rowland,

Matthew D’Antuono,

Anna Jermakowicz

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108349 - 108349

Published: Feb. 1, 2025

Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with fatal prognosis. This due in part to metabolic reprogramming allows tumors evade treatment. Therefore, we must uncover the pathways mediating these adaptations develop novel and effective treatments. We searched for genes are essential GBM cells as measured by whole-genome pan-cancer CRISPR screen available from DepMap identified methionine metabolism MAT2A AHCY. conducted genetic knockdown, evaluated mitochondrial respiration, performed targeted metabolomics study function of GBM. demonstrate or AHCY knockdown induces oxidative stress, hinders cellular reduces survival cells. Furthermore, selective MAT2a inhibition cell viability, impairs metabolism, shifts profile towards stress death. Mechanistically, regulate spare respiratory capacity, redox buffer cystathionine, lipid amino acid prevent damage Our results point pathway vulnerability Significance demonstrated maintains antioxidant production facilitate pro-tumorigenic ROS signaling survival. Importantly, targeting this has potential reduce growth improve patients.

Language: Английский

Citations

0
Mechanistic role of environmental toxicants in inducing cellular ferroptosis and its associated diseases DOI
Hong Chen,

Bingchun Liu,

Peixin Xu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 298, P. 118269 - 118269

Published: May 10, 2025

Language: Английский

Citations

0
MAT2a and AHCY Inhibition Disrupts Antioxidant Metabolism and Reduces Glioblastoma Cell Survival DOI Creative Commons
Emma Rowland, Matthew D’Antuono,

Anna Jermakowicz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 24, 2024

Abstract Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with fatal prognosis. This due in part to metabolic reprogramming allows tumors evade treatment. We therefore must uncover the pathways mediating these adaptations develop novel and effective treatments. searched for genes are essential GBM cells as measured by whole-genome pan-cancer CRISPR screen available from DepMap identified methionine metabolism MAT2A AHCY . conducted genetic knockdown, evaluated mitochondrial respiration, performed targeted metabolomics study function of GBM. demonstrate or knockdown induces oxidative stress, hinders cellular reduces survival cells. Furthermore, selective MAT2a inhibition cell viability, impairs metabolism, changes profile towards stress death. Mechanistically, regulates spare respiratory capacity, redox buffer cystathionine, lipid amino acid prevents DNA damage Our results point pathway vulnerability Significance demonstrated maintains antioxidant production facilitate pro-tumorigenic ROS signaling survival. Importantly, targeting this can potentially reduce growth improve patients.

Language: Английский

Citations

0