ArticleCancer biology & therapy2011
DNA mismatch repair proficiency executing 5-fluorouracil cytotoxicity in colorectal cancer cells.
Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Neoadjuvant immune checkpoint inhibitors for localized dMMR/MSI-H gastric cancer: a meta-analysis.ESMO open · 2026Pooled it
- Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.British journal of cancer · 2022Trial
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- Inflammation Drives Phosphorylation and Acetylation of MutS Homolog 3 and Interaction with Cytosolic HDAC6.Journal of Cancer · 2026Article
- Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells.Cellular and molecular life sciences : CMLS · 2024Article
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.BMC cancer · 2021Article
- Article
- Racial and ethnic disparities in colorectal cancer incidence and mortality.Advances in cancer research · 2021Article
- DNA mismatch repair is not disrupted in stage 0 colorectal cancer resected using endoscopic submucosal dissection.Oncology letters · 2020Article
- Tetranucleotide Microsatellite Mutational Behavior Assessed in Real Time: Implications for Future Microsatellite Panels.Cellular and molecular gastroenterology and hepatology · 2020Article
- MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression.Journal of biosciences · 2020Article
- Immunological Features with DNA Microsatellite Alterations in Patients with Colorectal Cancer.Journal of cancer immunology · 2020Article
- Exploiting DNA repair defects in colorectal cancer.Molecular oncology · 2019Review
- Article
- Clinical and Genetic Factors to Inform Reducing Colorectal Cancer Disparitites in African Americans.Frontiers in oncology · 2018Review
- Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy.Oncotarget · 2017Article
- An active molecule fromOncology letters · 2017Article
- Microsatellite Instability Pathway and EMAST in Colorectal Cancer.Current colorectal cancer reports · 2017Article
- Mismatch Repair Protein hMLH1, but not hMSH2, Enhances Estrogen-Induced Apoptosis of Colon Cancer Cells.Journal of Cancer · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background5-fluorouracil (5FU)-based chemotherapy is the standard treatment for advanced stage colorectal cancer (CRC) patients. Several groups including ours have reported that stage II-III colorectal cancer patients whose tumors retain DNA Mismatch repair (MMR) function derive a benefit from 5FU, but patients with tumors that lost MMR function do not. Although MMR recognition of 5FU incorporated in DNA has been demonstrated biochemically, it has not been demonstrated within cells to execute 5FU cytotoxicity.
aimTo establish an efficient construction model for 5FU within DNA and demonstrate that 5FU incorporated into DNA can trigger cellular cytotoxicity executed by the DNA MMR system.
methodsWe constructed a 5FdU-containing heteroduplex plasmid (5FdU plasmid) and 5FdU-containing linear dsDNA (5FdU linear DNA), and transfected these into MMR-proficient, hMLH1-/- and hMSH6-/- cells. We observed cell growth characteristics of both transfectants for 5FU-induced cytotoxicity.
resultsMMR- proficient cells transfected with the 5FdU plasmid but not the 5FdU linear DNA showed reduced cell proliferation by MTS and clonogenic assays, and demonstrated cell morphological change consistent with apoptosis. In MMR-deficient cells, neither the 5FdU plasmid nor 5FdU linear DNA induced cell growth or morphological changes different from controls.
conclusion5FdU as heteroduplex DNA in plasmid but not linear form triggered cytotoxicity in a MMR-dependent manner. Thus 5FU incorporated into DNA, separated from its effects on RNA, can be recognized by DNA MMR to trigger cell death.
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Registered trials
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