ArticleThe Journal of biological chemistry2012
Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 96 citations in OpenAlex.
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- Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions.International journal of molecular sciences · 2021Review
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- Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Pharmacological inhibition of p38 potentiates antimicrobial peptide TP4-induced cell death in glioblastoma cells.Molecular and cellular biochemistry · 2020Article
- Synthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent.Scientific reports · 2019Article
- p21cip1/waf1 Coordinate Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress.Cancers · 2019Review
- A Novel Polyhalogenated Monoterpene Induces Cell Cycle Arrest and Apoptosis in Breast Cancer Cells.Marine drugs · 2019Article
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Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer cell lines, suggesting a cell-specific response. We also found that cells undergoing p21-dependent cell death had higher sensitivity to oxidants and a specific pattern of mitochondrial polarization changes. Consistent with this, apoptosis could be blocked with targeted expression of catalase in the mitochondria of these cells. We propose that the balance between cancer cell death and arrest after p21 up-regulation depends on the specific effects of p21-induced ROS on the mitochondria. This suggests that selective up-regulation of p21 in cancer cells could be a successful therapeutic intervention for sarcomas and tumors with lower resistance to mitochondrial oxidative damage, regardless of p53 status.
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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.