ArticleCell death & disease2015
Reactive oxygen species and p21Waf1/Cip1 are both essential for p53-mediated senescence of head and neck cancer cells.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 79 citations in OpenAlex.
- Cellular senescence in renal ischemia-reperfusion injury.Chinese medical journal · 2025Review
- Beyond polarization: macrophage senescence in immunoregulation and cancer therapy.International journal of biological sciences · 2025Review
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- Regulation of endothelial ferroptosis by SESN1 in atherosclerosis and its related mechanism.Aging · 2023Article
- Integrated analysis of circRNA-associated ceRNA network in ischemic stroke.Frontiers in genetics · 2023Article
- Gain of Function (GOF) Mutant p53 in Cancer-Current Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence.Antioxidants (Basel, Switzerland) · 2022Article
- Observational
- Acute ischemic stroke triggers a cellular senescence-associated secretory phenotype.Scientific reports · 2021Article
- Impact of Acrylamide on Cellular Senescence Response and Cell Cycle Distribution via an In-vitro Study.Iranian journal of pharmaceutical research : IJPR · 2021Article
- Review
- The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation.Radiation research · 2020Review
- miR-106b-5p promotes cell proliferation and cell cycle progression by directly targeting CDKN1A in osteosarcoma.Experimental and therapeutic medicine · 2020Article
- Influence of the human papillomavirus on the radio-responsiveness of cancer stem cells in head and neck cancers.Scientific reports · 2020Article
- Expression of p16 and p21 in the frontal association cortex of ALS/MND brains suggests neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease.Neuropathology and applied neurobiology · 2020Article
- ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer.Oxidative medicine and cellular longevity · 2020Review
- COTI-2, A Novel Thiosemicarbazone Derivative, Exhibits Antitumor Activity in HNSCC through p53-dependent and -independent Mechanisms.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- A dynamic view of chemotherapy effectiveness.Nature · 2019Article
- Clinical update on head and neck cancer: molecular biology and ongoing challenges.Cell death & disease · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Treatment of head and neck squamous cell carcinoma, HNSCC, often requires multimodal therapy, including radiation therapy. The efficacy of radiotherapy in controlling locoregional recurrence, the most frequent cause of death from HNSCC, is critically important for patient survival. One potential biomarker to determine radioresistance is TP53 whose alterations are predictive of poor radiation response. DNA-damaging reactive oxygen species (ROS) are a by-product of ionizing radiation that lead to the activation of p53, transcription of p21(cip1/waf1) and, in the case of wild-type TP53 HNSCC cells, cause senescence. The expression of p21 and production of ROS have been associated with the induction of cellular senescence, but the intricate relationship between p21 and ROS and how they work together to induce senescence remains elusive. For the first time, we show that persistent exposure to low levels of the ROS, hydrogen peroxide, leads to the long-term expression of p21 in HNSCC cells with a partially functional TP53, resulting in senescence. We conclude that the level of ROS is crucial in initiating p53's transcription of p21 leading to senescence. It is p21's ability to sustain elevated levels of ROS, in turn, that allows for a long-term oxidative stress, and ensures an active p53-p21-ROS signaling loop. Our data offer a rationale to consider the use of either ROS inducing agents or therapies that increase p21 expression in combination with radiation as approaches in cancer therapy and emphasizes the importance of considering TP53 status when selecting a patient's treatment options.
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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.