5-Fluorouridine is a ribonucleotide metabolite of 5-Fluorouracil with anticancer activity[1]. 5-Fluorouridine can mark active transcription sites of cells in vivo and in vitro for immunodetection of nascent RNA[2, 3]. 5-Fluorouridine is an organofluorine compound belonging to pyrimidine nucleosides and their analogs. It is uridine with a fluorine substituent at the 5th position of the uracil ring and has a mutagenic effect[4].
In vitro, 5-Fluorouridine (10µM) treatment of HCT-116 cells for 24h increased the percentage of apoptotic cells, affected the expression of 1200 different genes during apoptosis, and increased the expression of macrophage inhibitory cytokine 1 (MIC-1) by up to 100-fold[5]. 5-Fluorouridine (167μM) treatment of gastric cancer cells (MKN45 and MKN28 cells) for 24-96h inhibited cell proliferation in a time-dependent manner[6].
In vivo, 5-Fluorouridine (567-1500mg/kg/day) was intraperitoneally injected into male CBA/J mice for 20 days, which induced gastrointestinal toxicity in mice[7].
References:
[1]Ghoshal K, Jacob S T. An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug[J]. Biochemical pharmacology, 1997, 53(11): 1569-1575.
[2]Puente-Bedia A, Berciano M T, Tapia O, et al. Nuclear reorganization in hippocampal granule cell neurons from a mouse model of Down syndrome: changes in chromatin configuration, nucleoli and Cajal bodies[J]. International Journal of Molecular Sciences, 2021, 22(3): 1259.
[3]Awasthi S, Verma M, Mahesh A, et al. DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA[J]. Nucleic Acids Research, 2018, 46(12): 6304-6317.
[4]Gmeiner W H. Chemistry of fluorinated pyrimidines in the era of personalized medicine[J]. Molecules, 2020, 25(15): 3438.
[5]Schmittgen T D, Gissel K A, Zakrajsek B A, et al. Diverse gene expression pattern during 5-fluorouridine-induced apoptosis[J]. International journal of oncology, 2005, 27(2): 297-306.
[6]Wu F, Li R T, Yang M, et al. Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2′-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics[J]. Cancer Letters, 2015, 363(1): 7-16.
[7]Houghton J A, Houghton P J, Wooten R S. Mechanism of induction of gastrointestinal toxicity in the mouse by 5-fluorouracil, 5-fluorouridine, and 5-fluoro-2′-deoxyuridine[J]. Cancer research, 1979, 39(7_Part_1): 2406-2413.
5-Fluorouridine是5-氟尿嘧啶（5-Fluorouracil）的核糖核苷酸代谢物，具有抗癌活性[1]。5-Fluorouridine可在体内和体外标记细胞的活性转录位点，用于新生RNA的免疫检测[2, 3]。5-Fluorouridine是一种有机氟化合物，属于嘧啶核苷及其类似物，是尿嘧啶环上5位带有氟取代基的尿苷，具有诱变剂的作用[4]。
在体外，5-Fluorouridine（10µM）处理HCT-116细胞24h，增加了凋亡细胞百分比，影响了细胞凋亡期间1200种不同基因的表达，使巨噬细胞抑制性细胞因子1（MIC-1）的表达增加了高达100倍[5]。5-Fluorouridine（167μM）处理胃癌细胞（MKN45和MKN28细胞）24-96h，以时间依赖性方式抑制了细胞增殖[6]。
在体内，5-Fluorouridine（567-1500mg/kg/day）通过腹腔注射处理雄性CBA/J小鼠20天，诱导了小鼠胃肠道毒性[7]。