ArticleBioMed research international2018
Caffeine Sensitizes U87-MG Human Glioblastoma Cells to Temozolomide through Mitotic Catastrophe by Impeding G2 Arrest.
Article in BioMed research international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Functional instant tea from black tea waste fiber: effects of extraction conditions on bioactive composition andFrontiers in nutrition · 2026Article
- Plant Alkaloids as Promising Anticancer Compounds with Blood-Brain Barrier Penetration in the Treatment of Glioblastoma: In Vitro and In Vivo Models.Molecules (Basel, Switzerland) · 2025Review
- Potential of Natural Products in the Treatment of Glioma: Focus on Molecular Mechanisms.Cell biochemistry and biophysics · 2024Review
- Caffeine: A Multifunctional Efficacious Molecule with Diverse Health Implications and Emerging Delivery Systems.International journal of molecular sciences · 2024Review
- Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells.Pharmaceutics · 2024Article
- Caffeine and neonatal acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Review
- Temozolomide protects against the progression of glioblastoma via SOX4 downregulation by inhibiting the LINC00470-mediated transcription factor EGR2.CNS neuroscience & therapeutics · 2023Article
- Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.Metabolites · 2022Review
- Cyclooxygenase-2 Upregulated by Temozolomide in Glioblastoma Cells Is Shuttled In Extracellular Vesicles Modifying Recipient Cell Phenotype.Frontiers in oncology · 2022Article
- Synergistic Effects of Taurine and Temozolomide Via Cell Proliferation Inhibition and Apoptotic Induction on U-251 MG Human Glioblastoma Cells.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines.Veterinary medicine and science · 2021Article
- Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review.Brain sciences · 2021Review
- Advances in Research of Adult Gliomas.International journal of molecular sciences · 2021Review
- Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?Frontiers in neurology · 2021Review
- WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation.Molecular medicine (Cambridge, Mass.) · 2020Article
- Homotypic targeting and drug delivery in glioblastoma cells through cell membrane-coated boron nitride nanotubes.Materials & design · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temozolomide (TMZ) is the first-line chemotherapeutic agent in the treatment of glioblastoma multiforme (GBM). Despite its cytotoxic effect, TMZ also induces cell cycle arrest that may lead to the development of chemoresistance and eventual tumor recurrence. Caffeine, a widely consumed neurostimulant, shows anticancer activities and is reported to work synergistically with cisplatin and camptothecin. The present study aimed to investigate the effects and the mechanisms of action of caffeine used in combination with TMZ in U87-MG GBM cells. As anticipated, TMZ caused DNA damage mediated by the ATM/p53/p21 signaling pathway and induced significant G2 delay. Concurrent treatment with caffeine repressed proliferation and lowered clonogenic capacity on MTT and colony formation assays, respectively. Mechanistic study showed that coadministration of caffeine and TMZ suppressed the phosphorylation of ATM and p53 and downregulated p21 expression, thus releasing DNA-damaged cells from G2 arrest into premature mitosis. Cell cycle analysis demonstrated that the proportion of cells arrested in G2 phase decreased when caffeine was administered together with TMZ; at the same time, the amount of cells with micronucleation and multipolar spindle poles increased, indicative of enhanced mitotic cell death. Pretreatment of cells with caffeine further enhanced mitotic catastrophe development in combined treatment and sensitized cells to apoptosis when followed by TMZ alone. In conclusion, our study demonstrated that caffeine enhanced the efficacy of TMZ through mitotic cell death by impeding ATM/p53/p21-mediated G2 arrest.
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