ArticleOncotarget2016
Acrolein preferentially damages nucleolus eliciting ribosomal stress and apoptosis in human cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Transcriptomic Analysis Identifies Acrolein Exposure-Related Pathways and Constructs a Prognostic Model in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- TP53 mutations and MDM2 polymorphisms in breast and ovarian cancers: amelioration by drugs and natural compounds.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Downregulation of rRNA synthesis by BCL-2 induces chemoresistance in diffuse large B cell lymphoma.iScience · 2025Article
- Ribosome biogenesis rate, a parameter of sensitivity to chemotherapeutic drugs inhibiting rRNA synthesis.Oncology reviews · 2025Review
- EnterohemorrhagicInfection and immunity · 2024Article
- Effect of Hydralazine on Angiotensin II-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Deficient Mice.International journal of molecular sciences · 2023Article
- Nucleolar stress: Molecular mechanisms and related human diseases.Cancer science · 2023Review
- Revisiting treatment-related cardiotoxicity in patients with malignant lymphoma-a review and prospects for the future.Frontiers in cardiovascular medicine · 2023Review
- Effect of heated tobacco products and traditional cigarettes on pulmonary toxicity and SARS-CoV-2-induced lung injury.Toxicology · 2022Article
- Receptor-Interacting Protein 140 Enhanced Temozolomide-Induced Cellular Apoptosis Through Regulation of E2F1 in Human Glioma Cell Lines.Neuromolecular medicine · 2022Article
- Critical Review on Fatty Acid-Based Food and Nutraceuticals as Supporting Therapy in Cancer.International journal of molecular sciences · 2022Review
- Downregulated RRS1 inhibits invasion and metastasis of BT549 through RPL11‑c‑Myc‑SNAIL axis.International journal of oncology · 2022Article
- Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus.Cells · 2021Review
- Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway.Scientific reports · 2021Article
- Triptolide interrupts rRNA synthesis and induces the RPL23‑MDM2‑p53 pathway to repress lung cancer cells.Oncology reports · 2020Article
- Identification of acrolein metabolites in human buccal cells, blood, and urine after consumption of commercial fried food.Food science & nutrition · 2019Article
- The nucleolus, an ally, and an enemy of cancer cells.Histochemistry and cell biology · 2018Review
- Treating hematological malignancies with drugs inhibiting ribosome biogenesis: when and why.Journal of hematology & oncology · 2018Review
- Nucleolar Stress: hallmarks, sensing mechanism and diseases.Cell stress · 2018Review
- Acrolein induces mtDNA damages, mitochondrial fission and mitophagy in human lung cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA). Acr triggers ribosomal stress responses, inhibits rRNA synthesis, reduces RNA polymerase I binding to the promoter of rRNA gene, disrupts nucleolar integrity, and impairs ribosome biogenesis and polysome formation. Acr causes an increase in MDM2 levels and phosphorylation of MDM2 in A549 and HeLa cells which are p53 active and p53 inactive, respectively. It enhances the binding of ribosomal protein RPL11 to MDM2 and reduces the binding of p53 and E2F-1 to MDM2 resulting in stabilization/activation of p53 in A549 cells and degradation of E2F-1 in A549 and HeLa cells. We propose that Acr induces ribosomal stress which leads to activation of MDM2 and RPL11-MDM2 binding, consequently, activates p53 and enhances E2F-1 degradation, and that taken together these two processes induce apoptosis and cell death.
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Registered trials
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