ArticleCell death & disease2014
Antioxidants decrease the apoptotic effect of 5-Fu in colon cancer by regulating Src-dependent caspase-7 phosphorylation.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 85 citations in OpenAlex.
- Phase II Study of 5-Fluorouracil, Oxaliplatin plus Dasatinib (FOLFOX-D) in First-Line Metastatic Pancreatic Adenocarcinoma.The oncologist · 2021Trial
- BMX-001 acts as a selective chemoradioprotector in rectal cancer.Redox biochemistry and chemistry · 2026Article
- Redox processes in the treatment of advanced skin cancers.Clinical & experimental metastasis · 2026Review
- Targeting SRC enhances differentiation and promotes multifaceted cell death mechanisms in recurrent group 3 medulloblastoma.Cell death & disease · 2026Article
- Exploring the Potential Mechanisms of Danshen for the Treatment of Ulcerative Colitis based on Serum Pharmacochemistry, Gene Expression Profiling, and Network Pharmacology: Regulation of Cell Apoptosis and Inflammatory Response.Current computer-aided drug design · 2026Article
- Biliverdin reductase B as a new target in breast cancer.Breast cancer research : BCR · 2025Article
- ELMOD2 Overexpression Predicts Adverse Outcomes and Regulates Tumor Progression in Gliomas.Current medical science · 2025Article
- Protective effects of ascorbic acid against anticancer drug-induced oxidative stress and genotoxic damage in3 Biotech · 2025Article
- Peroxisomal membrane protein PMP70 confers drug resistance in colorectal cancer.Cell death & disease · 2025Article
- A Preclinical Study on 4-Methyl-N-((4-(trifluoromethoxy)phenyl) carbamoyl)-benzenesulfonamide as a Potent Chemotherapeutic Agent against Liver and Pancreatic Carcinogenesis in Rats: Immunohistochemical and Histopathological Studies.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- A minimalist multifunctional nano-prodrug for drug resistance reverse and integration with PD-L1 mAb for enhanced immunotherapy of hepatocellular carcinoma.Journal of nanobiotechnology · 2024Article
- Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- The Salmon Oil OmeGo Reduces Viability of Colorectal Cancer Cells and Potentiates the Anti-Cancer Effect of 5-FU.Marine drugs · 2023Article
- Recent advances in the role of endogenous hydrogen sulphide in cancer cells.Cell proliferation · 2023Review
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- Managing life-threatening 5-fluorouracil cardiotoxicity.BMJ case reports · 2022Article
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- Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma.Journal of nanobiotechnology · 2021Article
- Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance.Redox biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Although the rate of development of drug resistance remains very high, 5-fluorouracil (5-Fu) is still the most common chemotherapeutic drug used for the treatment of colon cancer. A better understanding of the mechanism of why cancers develop resistance to 5-Fu could improve its therapeutic effect. Sometimes, antioxidants are used simultaneously with 5-Fu treatment. However, a recent clinical trial showed no advantage or even a harmful effect of combining antioxidants with 5-Fu compared with administration of 5-Fu alone. The mechanism explaining this phenomenon is still poorly understood. In this study, we show that 5-Fu can induce reactive oxygen species-dependent Src activation in colon cancer cells. Mouse embryonic fibroblasts that are deficient in Src showed a clear resistance to 5-Fu, and knocking down Src protein expression in colon cancer cells also decreased 5-Fu-induced apoptosis. We found that Src could interact with and phosphorylate caspase-7 at multiple tyrosine sites. Functionally, the tyrosine phosphorylation of caspase-7 increases its activity, thereby enhancing cellular apoptosis. When using 5-Fu and antioxidants together, Src activation was blocked, resulting in decreased 5-Fu-induced apoptosis. Our results provide a novel explanation as to why 5-Fu is not effective in combination with some antioxidants in colon cancer patients, which is important for clinical chemotherapy.
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