Abstract:
: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.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
da Silva EFG,Lima KG,Krause GC,Haute GV,Pedrazza L,Catarina AV,Gassen RB,de Souza Basso B,Dias HB,Luft C,Garcia MCR,Costa BP,Antunes GL,Basso LA,Donadio MVF,Machado P,de Oliveira JRdoi
10.1007/s10637-020-00941-2subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1653-1663issue
6eissn
0167-6997issn
1573-0646pii
10.1007/s10637-020-00941-2journal_volume
38pub_type
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