Brandl, Noah and Seitz, Rebecca and Sendtner, Noah and Mueller, Martina and Gülow, Karsten (2025) Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target. ANTIOXIDANTS, 14 (8): 1002. ISSN 2076-3921
Full text not available from this repository. (Request a copy)Abstract
Reactive oxygen species (ROS) act as double-edged swords in cancer biology-facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-kappa B, STAT3, and HIF-1 alpha. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; OXIDATIVE SIGNALING ORGANELLES; PROTEIN-TYROSINE PHOSPHATASES; OXYGEN SPECIES ROS; REACTIVE OXYGEN; REDOX-REGULATION; HYDROGEN-PEROXIDE; THIOREDOXIN REDUCTASE; SUPEROXIDE-DISMUTASE; reactive oxygen species (ROS); redox signaling; antioxidant defense; cancer metabolism; cancer therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Sep 2026 09:29 |
| Last Modified: | 22 Sep 2026 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66218 |
Actions (login required)
 |
View Item |
