ArticleBMC cancer2019
Caffeine citrate enhanced cisplatin antitumor effects in osteosarcoma and fibrosarcoma in vitro and in vivo.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
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- Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages.Pharmaceuticals (Basel, Switzerland) · 2023Review
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- Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.The Journal of clinical investigation · 2022Article
- Recent Progress in the Study of Taste Characteristics and the Nutrition and Health Properties of Organic Acids in Foods.Foods (Basel, Switzerland) · 2022Review
- Effects of dihydroartemisinin combined with cisplatin on proliferation, apoptosis and migration of HepG2 cells.Oncology letters · 2022Article
- How Phosphofructokinase-1 Promotes PI3K and YAP/TAZ in Cancer: Therapeutic Perspectives.Cancers · 2022Article
- Tannic acid enhances cisplatin effect on cell proliferation and apoptosis of human osteosarcoma cell line (U2OS).Pharmacological reports : PR · 2022Article
- Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update.International journal of molecular sciences · 2021Review
- Article
- Upregulation of cell division cycle 20 in cisplatin resistance-induced epithelial-mesenchymal transition in osteosarcoma cells.American journal of translational research · 2020Article
- Establishment of a Jaw Fibrosarcoma Patient-Derived Xenograft and Evaluation of the Tumor Suppression Efficacy of Plumbagin Against Jaw Fibrosarcoma.Frontiers in oncology · 2020Article
- Co-expression network analysis identifies a gene signature as a predictive biomarker for energy metabolism in osteosarcoma.Cancer cell international · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile multiagent chemotherapy has dramatically improved the prognosis of sarcoma, the novel chemotherapeutics have hardly developed over the past 30 years. Caffeine can induce apoptosis, delays in cell cycle progression and can enhance the cytocidal effects of anti-cancer agents. Citrate has been reported to enhance the cytocidal effect of cisplatin in gastric cancer in vitro. However its effect in sarcoma cells had not been reported.
methodsThis study was designed to evaluate whether the addition of caffeine, citrate, or caffeine citrate to cisplatin improved its cytocidal effect (cell survival, proliferation, and apoptosis) on human osteosarcoma (HOS), human fibrosarcoma (HT1080) and murine osteosarcoma (LM8) cell lines. We also tested the various combinations in a mouse heterotopic transplantation model in vivo. In cell survival assay, combination index (CI) of caffeine citrate was calculated as a combination of anhydrous caffeine and citric acid, and the synergy was evaluated (CI < 1.0).
resultsIn all cell lines, cisplatin combined with caffeine citrate significantly reinforced the anticancer effect compared with cisplatin alone, combination of cisplatin and anhydrous caffeine, and combination of cisplatin and citric acid. Moreover, CI was < 1.0 in all conditions. The anticancer agent reinforcement effect of caffeine citrate was synergy of anhydrous caffeine and citric acid. In cell proliferation and cell cycle assay revealed that caffeine citrate had most strong effect as a combination drug than caffeine and citric acid in inducing G0/G1 cell-cycle arrest with subsequent suppressed cell proliferation. In mitochondrial depolarization and caspase 3/7 activity assay revealed that caffeine citrate had most strong effect as a combination drug than caffeine and citric acid in apoptosis associated with decreased mitochondrial membrane potential. In vivo, three different drug concentrations were tested, and cisplatin combined with caffeine citrate was found to have the strongest antitumor effect.
conclusionsThis is the first report demonstrating that caffeine citrate has a significantly greater potentiating effect on cisplatin than adding either caffeine or citric acid. The combination of cisplatin with caffeine citrate is a novel treatment that might hold promise for improving the outcome of osteosarcoma and fibrosarcoma, which up till now has generally not responded well to chemotherapy.
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