ArticlePloS one2021
Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 26 citations in OpenAlex.
- Hesperidin and Hesperetin: Epigenetic-Stemness Crosstalk, Antitumor Mechanisms, Preclinical Data and Translation Barriers.Biomolecules · 2026Review
- Drug Repurposing in Veterinary Oncology: Myth or Reality?Veterinary sciences · 2025Review
- Dissecting the role of metformin in urogenital malignancies.Annals of medicine and surgery (2012) · 2025Article
- Repurposing of Metformin to Improve Survival Outcomes in Patients With Upper Tract Urothelial Carcinoma.Cancer medicine · 2025Article
- Multimodal Blockade of the Renin-Angiotensin System in the Treatment of Cancer in Dogs Has Mild Adverse Effects in Some Dogs.Veterinary sciences · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Metformin: A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation.Journal of pharmaceutical analysis · 2024Article
- Genetic effect of metformin use on risk of cancers: evidence from Mendelian randomization analysis.Diabetology & metabolic syndrome · 2023Article
- High risk of non-cancer mortality in bladder cancer patients: evidence from SEER-Medicaid.Journal of cancer research and clinical oncology · 2023Article
- Repurposing Drugs in Small Animal Oncology.Animals : an open access journal from MDPI · 2022Review
- Updates on the Pivotal Roles of Mitochondria in Urothelial Carcinoma.Biomedicines · 2022Review
- Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox‑LDL‑induced THP‑1 monocytes.Experimental and therapeutic medicine · 2022Article
- The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models.Biomolecules · 2022Review
- Characteristics and Applications of Canine In Vitro Models of Bladder Cancer in Veterinary Medicine: An Up-to-Date Mini Review.Animals : an open access journal from MDPI · 2022Review
- Heterogeneous Expression and Subcellular Localization of Pyruvate Dehydrogenase Complex in Prostate Cancer.Frontiers in oncology · 2022Article
- Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesotheliomaFrontiers in pharmacology · 2022Article
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Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases is promising for new antineoplastic therapies. Sodium dichloroacetate (DCA) reactivates oxidative phosphorylation in the cancer cell mitochondria, reducing apoptosis resistance in cancer cells. Furthermore, metformin inhibits the proliferation of tumor cells and CD133+ cancer -stem-like cells. In the present study, we evaluated the independent and synergistic effect of metformin and DCA on the metabolic activity, cell proliferation, and apoptosis of a canine prostate adenocarcinoma (Adcarc1258) and a transitional cell carcinoma cell line (TCC1506) in comparison to a primary canine fibroblast culture. Determining metformin uptake in tumor cells was performed by quantitative HPLC. Depending on the dosage, metformin as a single agent inhibited the metabolic activity and cell proliferation of the tumor cells, showing only minor effects on the fibroblasts. Furthermore, 1 mM metformin increased apoptosis over 96 h in the tumor cell lines but not in fibroblasts. Additionally, metformin uptake into the tumor cells in vitro was measurable by quantitative HPLC. Synergistic effects for the combination therapy were observed in both neoplastic cell lines as well as in the fibroblasts. Based on these results, metformin might be a promising therapeutic agent for canine urogenital tumors. Further studies on kinetics, toxicology, bioavailability, and application of metformin in dogs are necessary.
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