Flucytosine (5-FC, 5-Fluorocytosine) is a synthetic antimycotic compound. In combination with amphotericin B, 5-FC can be used to treat severe systemic mycoses, such as cryptococcosis, candidosis, chromoblastomycosis and aspergillosis. Moreover, 5-FC has been combined with newer azole antifungal agents; it also plays an important role in a new approach to the treatment of cancer. The severe side effects of 5-FC include hepatotoxicity and bone-marrow depression[3]. 5-FC half-life in the serum of 10 rabbits increased from 3.35 +/- 0.27 to 24.63 +/- 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 mug/ml and were 74.4 +/- 5.6% of simultaneously determined serum concentrations[4]. The 5FC-FCZ (fluconazole, FCZ) combination was antagonistic against Candida species, but for some Candida isolates synergism was found. For C. neoformans the interaction for both combinations was highly dependent on the tested isolate and the method used[5].
5-Fluorocytosine/5-氟胞嘧啶 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H9 human embryonic stem cells
50 µM
36 h
To verify the cytotoxic effect of 5-FC on H9 human embryonic stem cells, results showed no significant toxicity at 50 µM concentration
Exp Mol Med. 2019 Jul 19;51(7):1-12
293T cells
50 µM
48 h
To verify the cytotoxic effect of 5-FC on 293T cells, results showed no significant toxicity at 50 µM concentration
Exp Mol Med. 2019 Jul 19;51(7):1-12
R3327-AT cells
100 µg/ml
24 h
To evaluate the cytotoxicity of 5-FC and 5-FU on R3327-AT cells. Results showed that CDUPRT-expressing cells were more sensitive to 5-FC and 5-FU than CD-expressing cells.
Radiother Oncol. 2009 Sep;92(3):345-52
T24 bladder epithelial cells
10 µg/mL
30 min
To evaluate the effect of 5-FC on KTE223 strain adhesion to bladder epithelial cells. Results showed that 5-FC reduced adhesion in a dose-dependent manner and slightly increased epithelial cell survival.
To assess the effect of 5-FC on virulence factor expression in the KTE223 strain. Results showed that 5-FC significantly inhibited the expression of csgB and csgD genes, indicating its impact on biofilm formation through pyrimidine starvation.
To evaluate the effect of 5-FC on biofilm formation and adhesion in UPEC strains. Results showed that 5-FC significantly reduced biofilm adhesion of UPEC clinical isolates at both 30°C and 37°C.
To evaluate the effect of 5-FC on CD-expressing stem cell growth, results showed significant inhibition of HB1.F3.CD cell growth
Cancer Sci. 2010 Apr;101(4):955-62
SKOV-3 cells
1, 10, 100 µg/mL
4 days
To evaluate the effect of 5-FC on ovarian cancer cell growth, results showed no significant inhibition of SKOV-3 cell growth at tested concentrations
Cancer Sci. 2010 Apr;101(4):955-62
MCF-7 human breast cancer cells
2 mM
72 h
To investigate the cytotoxicity of 5-FC in the presence of UC-ACD on MCF-7 cells.
ACS Nano. 2022 Oct 25;16(10):15873-15883
Caco-2 human colorectal cancer cells
2 mM
72 h
To investigate the cytotoxicity of 5-FC in the presence of UC-ACD (conjugates of upconversion nanoparticles and anti-EGFR affibody-cytosine deaminase fusion proteins) on Caco-2 cells.
ACS Nano. 2022 Oct 25;16(10):15873-15883
Human prostate carcinoma cells DU145
0–30mM
6 days
To evaluate the sensitivity of DU145 cells transfected with wild-type and mutant bCD to 5FC, results showed that mutant bCD-transfected cells were 2.1–5-fold more sensitive to 5FC than wild-type.
Cancer Res. 2009 Jun 1;69(11):4791-9
Human colorectal carcinoma cells HCT116
0–30mM
6 days
To evaluate the sensitivity of HCT116 cells transfected with wild-type and mutant bCD to 5FC, results showed that mutant bCD-transfected cells were 2.4–17-fold more sensitive to 5FC than wild-type.
Cancer Res. 2009 Jun 1;69(11):4791-9
Rat C6 glioma cells
0–30mM
6 days
To evaluate the sensitivity of C6 cells transfected with wild-type and mutant bCD to 5FC, results showed that mutant bCD-transfected cells were 1.3–2.7-fold more sensitive to 5FC than wild-type.
Cancer Res. 2009 Jun 1;69(11):4791-9
Cryptococcus gattii VGII
300 mg/mL
To evaluate the adaptation of VGII strains to 5-fluorocytosine, finding that some VGII strains exhibited high adaptation to 5-fluorocytosine
Innovation (Camb). 2024 Jul 31;5(5):100681
5-Fluorocytosine/5-氟胞嘧啶 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male athymic nu/nu mice
Subcutaneous tumor model
Intravenous injection
150 mg/kg
Single dose, monitored for 2 hours
To monitor the metabolism of 5-FC and 5-FU using 19F MRS. Results showed that CDUPRT expression led to enhanced accumulation of fluorine nucleotide (FNuc) in vivo.
Radiother Oncol. 2009 Sep;92(3):345-52
C57BL/6 mice
Intracerebral infection with Cryptococcus neoformans
Intraperitoneal injection
100 mg/kg
Every other day for 28 days
Evaluate the efficacy of 5-FC combined with Amphotericin B. Results showed that all mice treated with AmpB + 5-FC survived until the end of the experiment, whereas only 33% of mice in the AmpB + PEA group survived.
Antimicrob Agents Chemother. 2023 Oct 18;67(10):e0045923
BALB/c athymic nude mice
Caco-2 tumor model
Oral gavage
10 mg/mL
Evaluate the tumor targeting and 5-FC conversion efficacy of UC-ACD in vivo. Results showed significantly slower tumor growth (2.2±0.04 - 2.5±0.16-fold) in UC-ACD (+)IR treated tumors, with median survival increasing from 28 to 35 days.
ACS Nano. 2022 Oct 25;16(10):15873-15883
Nude mice
HCT116 xenograft tumor model
Intraperitoneal injection
375mg/kg
Twice daily for 21 days
To evaluate the tumor growth inhibition of mutant bCD (1525) in vivo, results showed that 1525-expressing tumors were significantly restricted in growth under 5FC treatment, while wild-type bCD-expressing tumors were unresponsive to the same dose of 5FC.
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