ArticleCell death & disease2013
Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Drug-herb combination therapy in cancer management.Molecular biology reports · 2022Pooled it
- Molecular insights into triazole-based compounds for triple-negative breast cancer treatment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Innovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics.Discover oncology · 2026Review
- Everolimus destabilizes thymidylate synthase via suppressing its O-GlcNAcylation and sensitizes HER2-negative breast cancer to fluorouracil.Cell death & disease · 2026Article
- Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- ZIF-8 Nanocarrier-Based Co-Delivery of Curcumin and 5-Fluorouracil for Synergistic Antitumor Activity in Hepatocellular Carcinoma.International journal of general medicine · 2026Article
- Synergistic Effects of Mistletoe Lectin and Cisplatin on Triple-Negative Breast Cancer Cells: Insights from 2D and 3D In Vitro Models.International journal of molecular sciences · 2025Article
- Curcumin Administration Routes in Breast Cancer Treatment.International journal of molecular sciences · 2024Review
- Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.Pharmaceutics · 2024Review
- Harnessing the nutriceutics in early-stage breast cancer: mechanisms, combinational therapy, and drug delivery.Journal of nanobiotechnology · 2024Review
- The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management.Cancers · 2024Review
- Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer.Scientific reports · 2024Article
- Curcumin/L-OHP co-loaded HAP for cGAS-STING pathway activation to enhance the natural immune response in colorectal cancer.Bioengineering & translational medicine · 2024Article
- An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments.International journal of molecular sciences · 2023Review
- Recent Advances in Curcumin-Based Combination Nanomedicines for Cancer Therapy.Journal of functional biomaterials · 2023Review
- Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future.Pharmaceutics · 2023Review
- 5-FU and the dietary flavonoid carvacrol: a synergistic combination that induces apoptosis in MCF-7 breast cancer cells.Medical oncology (Northwood, London, England) · 2022Article
- A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health.Molecules (Basel, Switzerland) · 2022Review
- Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer.International journal of molecular sciences · 2022Review
- Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment.International journal of molecular sciences · 2021Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, we report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. We found that 10 μM 5-FU and 10 μM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-κB (NF-κB), and this observation was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-κB activation, whereas inactivation of NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates the activation of NF-κB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.
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Registered trials
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.