ArticleBiochemical pharmacology2012
Mitochondrial superoxide mediates doxorubicin-induced keratinocyte apoptosis through oxidative modification of ERK and Bcl-2 ubiquitination.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 93 citations in OpenAlex.
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- A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system.Nature biomedical engineering · 2025Article
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- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Oxidative Stress-Mediated Programmed Cell Death: a Potential Therapy Target for Atherosclerosis.Cardiovascular drugs and therapy · 2024Review
- [A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Phlorotannins: Novel Orally Administrated Bioactive Compounds That Induce Mitochondrial Dysfunction and Oxidative Stress in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
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- Effects of Cooling Interventions with Different Target Temperatures on Heat Stroke Rats.Journal of inflammation research · 2023Article
- Modulation of redox homeostasis: A strategy to overcome cancer drug resistance.Frontiers in pharmacology · 2023Review
- Thyme Oil and Thymol Counter Doxorubicin-Induced HepatotoxicityOxidative medicine and cellular longevity · 2022Article
- Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin.Frontiers in oncology · 2021Article
- Reactive Oxygen Species-Mediated Inflammation and Apoptosis in Hand-Foot Syndrome Induced by PEGylated Liposomal Doxorubicin.International journal of nanomedicine · 2021Article
- The double-edged roles of ROS in cancer prevention and therapy.Theranostics · 2021Review
- PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population.Frontiers in oncology · 2021Article
- The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy.International journal of molecular sciences · 2020Review
- SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Massive apoptosis of keratinocytes has been implicated in the pathogenesis of chemotherapy-induced skin toxicities, but the underlying mechanisms of action are not well understood. The present study investigated the apoptotic effect of doxorubicin (DOX) on HaCaT keratinocytes and determined the underlying mechanisms. Treatment of the cells with DOX induced reactive oxygen species (ROS) generation and a concomitant increase in apoptotic cell death through the mitochondrial death pathway independent of p53. Electron spin resonance and flow cytometry studies showed that superoxide is the primary oxidative species induced by DOX and responsible for the death inducing effect. Ectopic expression of mitochondrial superoxide scavenging enzyme (MnSOD) or treatment with MnSOD mimetic (MnTBAP) inhibited DOX-induced superoxide generation and apoptosis. The mechanism by which superoxide mediates the apoptotic effect of DOX was shown to involve downregulation of Bcl-2 through ubiquitin-proteasomal degradation. Superoxide induces dephosphorylation of Bcl-2 through MAP kinase ERK1/2 inactivation, which promotes ubiquitination of Bcl-2. We also provide evidence for the oxidative modification of ERK1/2 through cysteine sulfenic acid formation. These findings indicate a novel pathway for redox regulation of apoptosis regulatory proteins, which could be important in the understanding of chemotherapy-induced toxicities and development of preventive treatment strategies which are currently lacking.
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