ArticlePloS one2011
The chemotherapeutic drug 5-fluorouracil promotes PKR-mediated apoptosis in a p53-independent manner in colon and breast cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Targeting the epigenome and the integrated stress response to normalize colorectal cancer subclonal plasticity and progression.Cell death & disease · 2026Article
- Exploratory Proteomic Profiling Reveals Potential Mediators of 5-FU Response under p53 Deficiency in Colon Cancer Cells.Biomolecules & therapeutics · 2026Article
- Protective effects of ascorbic acid against anticancer drug-induced oxidative stress and genotoxic damage in3 Biotech · 2025Article
- Review
- PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation.Oncogene · 2022Article
- Combination effects of capecitabine, irinotecan and 17-AAG on colorectal cancer cell line (HT-29).Annals of medicine and surgery (2012) · 2022Article
- Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer.International journal of molecular sciences · 2022Review
- Article
- Hiding in Plain Sight: Formation and Function of Stress Granules During Microbial Infection of Mammalian Cells.Frontiers in molecular biosciences · 2021Review
- Targeting stress granules: A novel therapeutic strategy for human diseases.Pharmacological research · 2020Review
- Targeting Protein Synthesis in Colorectal Cancer.Cancers · 2020Review
- Article
- Understanding the roles of stress granule during chemotherapy for patients with malignant tumors.American journal of cancer research · 2020Review
- BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Activation of the PERK-ATF4 pathway promotes chemo-resistance in colon cancer cells.Scientific reports · 2019Article
- BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil.Therapeutic advances in medical oncology · 2019Article
- Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells.Scientific reports · 2018Article
- NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1 ratio.Cell death & disease · 2018Article
- PKR: A Kinase to Remember.Frontiers in molecular neuroscience · 2018Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug.
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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.