ArticleMedical oncology (Northwood, London, England)2019
Caffeine enhances the anti-tumor effect of 5-fluorouracil via increasing the production of reactive oxygen species in hepatocellular carcinoma.
Article in Medical oncology (Northwood, London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Glyceryl Trinitrate Enhances Caffeine Cytotoxicity Under Metabolic Stress in Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Molecular Insights into the Interaction Between Metformin and Caffeine: The Time-Dependent Antagonism and Modulation of p53 Signaling in Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Autophagy-Apoptosis synchronization: A mechanism of black grape anthocyanins mediated chemosensitization of 5-FU in HepG2 hepatocellular carcinoma cells.Medical oncology (Northwood, London, England) · 2025Article
- Article
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- Caffeine as a Modulator in Oncology: Mechanisms of Action and Potential for Adjuvant Therapy.International journal of molecular sciences · 2025Review
- Coffee as a Source of Antioxidants and an Elixir of Youth.Antioxidants (Basel, Switzerland) · 2025Review
- Evaluation of the Combined Effect of Caffeine and 5-Fluorouracil on Colorectal Cancer Cell Lines.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Phytochemicals as Potential Lead Molecules against Hepatocellular Carcinoma.Current medicinal chemistry · 2024Review
- Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation.Journal of inflammation research · 2024Review
- Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Elevation of Anticancer Drug Toxicity by Caffeine in Spheroid Model of Human Lung Adenocarcinoma A549 Cells Mediated by Reduction in Claudin-2 and Nrf2 Expression.International journal of molecular sciences · 2022Article
- Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance.Biomolecules & therapeutics · 2022Review
- Caffeine in liver diseases: Pharmacology and toxicology.Frontiers in pharmacology · 2022Review
- Caffeine Induces G0/G1 Cell Cycle Arrest and Inhibits Migration through Integrin αv, β3, and FAK/Akt/c-Myc Signaling Pathway.Molecules (Basel, Switzerland) · 2021Article
- Review
- Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.Nutrients · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The development of drug resistance affecting the prognosis of patients with hepatocellular carcinoma (HCC) leads to low survival rate of HCC patients. Caffeine is reported to have a function of protecting the liver and anti-tumor activity. Therefore, caffeine may be an ideal enhancer for HCC chemotherapy regimens. Our study showed that the combination of caffeine and 5-FU significantly inhibited the proliferation of HCC cells in vivo and in vitro comparing with caffeine or 5-FU monotherapy. The CI values of caffeine (0.5 mM) combined with 5-FU (25, 50 μM) were all less than 1, confirming that the utilization of drug combination has a synergistic inhibitory effect on the proliferation of HCC cells. Meanwhile, results of Western blot and TUNEL assays demonstrated that the apoptotic level of HCC cells in the combined group was significantly increased. The protein expression level of cleaved PARP was up-regulated, while the protein level of Bcl-2 and Bcl-xL was down-regulated. In addition, we found that ROS levels were increased in the 1 mM caffeine and 25 μM 5-FU combination group comparing with the control or single drug group. Taken together, this is the first study to demonstrate that the combination of caffeine and 5-FU inhibits HCC cells proliferation and promotes cellular apoptosis by regulating intracellular ROS production. The present data provides a basis for the application of caffeine combined with 5-FU as a novel chemotherapy regimen for HCC.
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