CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence
| Autor: | Pablo Machado, Bruno de Souza Basso, Bruna Pasqualotto Costa, Gabriela Viegas Haute, Leonardo Pedrazza, Luiz Augusto Basso, Géssica Luana Antunes, Kelly Goulart Lima, Carolina Luft, Jarbas Rodrigues de Oliveira, Maria Claudia Rosa Garcia, Henrique Bregolin Dias, Anderson Velasque Catarina, Márcio Vinícius Fagundes Donadio, Rodrigo Benedetti Gassen, Elisa Feller Gonçalves da Silva, Gabriele Catyana Krause |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Senescence Carcinoma Hepatocellular Cell cycle checkpoint Pyridines Antineoplastic Agents Apoptosis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Humans Pharmacology (medical) Uridine Cellular Senescence Uridine phosphorylase 1 Cell Proliferation Pharmacology Uridine Phosphorylase Chemistry Cell growth Liver Neoplasms Autophagy Cell Cycle Checkpoints Hep G2 Cells 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Leukocytes Mononuclear Cancer research Cisplatin Intracellular |
| Zdroj: | Investigational New Drugs. 38:1653-1663 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence. |
| Databáze: | OpenAIRE |
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