ArticleFree radical biology & medicine2019
Xanthine oxidase-mediated oxidative stress promotes cancer cell-specific apoptosis.
Article in Free radical biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Palmitic Acid-Induced Hepatotoxicity in Adult Zebrafish: Molecular Mechanisms and Advances in Intervention.Biology · 2026Review
- Protective effects of Tinospora crispa and Tinospora cordifolia extracts against methylglyoxal-induced oxidative stress and apoptosis in hFOB 1.19 cells: ELISA-based evaluation and molecular docking insights with antioxidant enzymes.BMC complementary medicine and therapies · 2026Article
- Alternol-Induced Oxidative Modification of SQSTM1/p62 Is Associated with Nrf2 Signaling and Autophagy-Related Responses in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- A powerful representation learning method for enhanced analysis of incomplete multi-omics data.NPJ systems biology and applications · 2026Article
- A sequentially targeted and pathology-responsive nanoplatform for synergistic treatment of dry eye disease via concurrent anti-inflammation and mitochondrial ROS scavenging.Journal of nanobiotechnology · 2026Article
- Immunometabolic Contributions of Atopobiaceae Family Members in Human Papillomavirus Infection, Cervical Dysplasia, and Cancer.The Journal of infectious diseases · 2025Article
- Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target.Antioxidants (Basel, Switzerland) · 2025Review
- Piperine Induces Apoptosis and Cell Cycle Arrest via Multiple Oxidative Stress Mechanisms and Regulation of PI3K/Akt and MAPK Signaling in Colorectal Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Biosocial Determinants of Health Among Patients with Chronic Liver Disease and Liver Cancer.Cancers · 2025Article
- Oatmeal and wheat flour as the sources of thyroid peroxidase and proinflammatory enzymes modulators in the prevention of thyroid diseases.Scientific reports · 2025Article
- Natural compound Alternol exerts a broad anti-cancer spectrum and a superior therapeutic safety indexFrontiers in pharmacology · 2024Article
- Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death.Frontiers in pharmacology · 2024Article
- Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.Neurosurgical review · 2023Article
- 5-Aminolevulinic acid combined with ferrous iron ameliorates scrotal heat stress-induced spermatogenic damage by enhancing HO-1 expression.Molecular biology reports · 2023Article
- Article
- Discovery of Hepatotoxic Equivalent Markers and Mechanism ofMolecules (Basel, Switzerland) · 2022Article
- The double faced role of xanthine oxidoreductase in cancer.Acta pharmacologica Sinica · 2022Review
- The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.Cell death & disease · 2022Review
- Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies.Biomedicines · 2022Review
- C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation.International journal of medical sciences · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The natural compound Alternol was shown to induce profound oxidative stress and apoptotic cell death preferentially in cancer cells. In this study, a comprehensive investigation was conducted to understand the mechanism for Alternol-induced ROS accumulation responsible for apoptotic cell death. Our data revealed that Alternol treatment moderately increased mitochondrial superoxide formation rate, but it was significantly lower than the total ROS positive cell population. Pre-treatment with mitochondria-specific anti-oxidant MitoQ, NOX or NOS specific inhibitors had no protective effect on Alternol-induced ROS accumulation and cell death. However, XDH/XO inhibition by specific small chemical inhibitors or gene silencing reduced total ROS levels and protected cells from apoptosis induced by Alternol. Further analysis revealed that Alternol treatment significantly enhanced XDH oxidative activity and induced a strong protein oxidation-related damage in malignant but not benign cells. Interestingly, benign cells exerted a strong spike in anti-oxidant SOD and catalase activities compared to malignant cells after Alternol treatment. Cell-based protein-ligand engagement and in-silicon docking analysis showed that Alternol interacts with XDH protein on the catalytic domain with two amino acid residues away from its substrate binding sites. Taken together, our data demonstrate that Alternol treatment enhances XDH oxidative activity, leading to ROS-dependent apoptotic cell death.
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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 OpenQuestion graph.