ArticleAmerican journal of physiology. Renal physiology2008
Cytoplasmic initiation of cisplatin cytotoxicity.
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 78 citations in OpenAlex.
- Artemisinin alleviates cisplatin-induced damage in GC-1 spermatogonia through ER stress mechanisms.Heliyon · 2025Article
- E2F-1-Akt1 Interaction as Precursor to Cisplatin-induced Apoptosis in Triple-negative Breast Cancer Cells.Oman medical journal · 2025Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells.Frontiers in pharmacology · 2024Review
- Revisiting the Anti-Cancer Toxicity of Clinically Approved Platinating Derivatives.International journal of molecular sciences · 2022Review
- Expression of large tumour suppressor (LATS) kinases modulates chemotherapy response in advanced non-small cell lung cancer.Translational lung cancer research · 2020Article
- G-Protein-Coupled Receptor 120 Mediates DHA-Induced Apoptosis by Regulating IP3R, ROS and, ER Stress Levels in Cisplatin-Resistant Cancer Cells.Molecules and cells · 2019Article
- Pt-induced crosslinks promote target enrichment and protection from serum nucleases.Journal of inorganic biochemistry · 2018Article
- The deficiency of CX3CL1/CX3CR1 system ameliorates high fructose diet-induced kidney injury by regulating NF-κB pathways in CX3CR1-knock out mice.International journal of molecular medicine · 2018Article
- Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin.Oncotarget · 2018Article
- Organic cation transporter 3 mediates cisplatin and copper cross-resistance in hepatoma cells.Oncotarget · 2018Article
- Article
- Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress.Oncotarget · 2017Article
- Akt/mTOR mediated induction of bystander effect signaling in a nucleus independent manner in irradiated human lung adenocarcinoma epithelial cells.Oncotarget · 2017Article
- Urinary TIMP2⋅IGFBP7 for the prediction of platinum-induced acute renal injury.International journal of nephrology and renovascular disease · 2017Article
- Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss.Frontiers in cellular neuroscience · 2017Review
- A Comprehensive Review on the Genetic Regulation of Cisplatin-induced Nephrotoxicity.Current genomics · 2016Article
- Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells.Molecular medicine reports · 2015Article
- Micheliolide overcomes KLF4-mediated cisplatin resistance in breast cancer cells by downregulating glutathione.OncoTargets and therapy · 2015Article
- Proteasome inhibitor lactacystin enhances cisplatin cytotoxicity by increasing endoplasmic reticulum stress-associated apoptosis in HeLa cells.Molecular medicine reports · 2015Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism of action of cisplatin as a chemotherapeutic agent has been attributed to DNA binding, while its mechanism of action as a nephrotoxin is unresolved. Only approximately 1% of intracellular cisplatin interacts with DNA, primarily forming intrastrand cross-linked adducts, and many studies have implicated both nuclear and cytoplasmic causes of cisplatin-induced death in cultured cells. We have demonstrated that cisplatin cytotoxicity depends on cdk2 activity, which is at least partly through the cdk2-E2F1 pathway. The mechanism of the dependency on cdk2, and whether cdk2 activation of E2F1 represents the only cell death pathway involved, is still unclear. Our previous work showed that deletion of the nuclear localization signal from p21 WAF1/CIP1, a cdk2 inhibitor, did not alter its protective action against cisplatin cytotoxicity. Active cdk2-cyclin complexes are localized in both the nucleus and cytoplasm, and it was reported that cdk2 translocated to the cytoplasm after an apoptotic stimulus. Herein, we show that cisplatin caused cell death in enucleated mouse kidney proximal tubule cells (TKPTS), which was prevented by cdk2 inhibition. Also, we localized cytoplasmic cdk2 to both the endoplasmic reticulum (ER) and Golgi compartments, and ER stress was blocked by specific cdk2 inhibition. We conclude that cisplatin can induce nuclear independent apoptosis, cisplatin cytotoxicity can be initiated by cytoplasmic events, and cytoplasmic cdk2 plays an important role in apoptosis signaling.
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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.