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CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

Authors :
da Silva, Elisa Feller Gonçalves
Lima, Kelly Goulart
Krause, Gabriele Catyana
Haute, Gabriela Viegas
Pedrazza, Leonardo
Catarina, Anderson Velasque
Gassen, Rodrigo Benedetti
de Souza Basso, Bruno
Dias, Henrique Bregolin
Luft, Carolina
Garcia, Maria Claudia Rosa
Costa, Bruna Pasqualotto
Antunes, Géssica Luana
Basso, Luiz Augusto
Donadio, Márcio Vinícius Fagundes
Machado, Pablo
de Oliveira, Jarbas Rodrigues
Source :
Investigational New Drugs; Dec2020, Vol. 38 Issue 6, p1653-1663, 11p
Publication Year :
2020

Abstract

Summary: 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01676997
Volume :
38
Issue :
6
Database :
Complementary Index
Journal :
Investigational New Drugs
Publication Type :
Academic Journal
Accession number :
146533697
Full Text :
https://doi.org/10.1007/s10637-020-00941-2