The metabolism of flubendazole in human liver and cancer cell lines
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10380296" target="_blank" >RIV/00216208:11160/18:10380296 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/18:10380296
Result on the web
<a href="http://onlinelibrary.wiley.com/doi/10.1002/dta.2369" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/dta.2369</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/dta.2369" target="_blank" >10.1002/dta.2369</a>
Alternative languages
Result language
angličtina
Original language name
The metabolism of flubendazole in human liver and cancer cell lines
Original language description
Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut-residing nematodes in humans. In addition, FLU is now considered a promising anti-cancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. Precision-cut human liver slices and 9 cell lines of different origin (breast, colon, oral cavity) were used as in vitro model systems. Our study showed that FLU with a reduced carbonyl group (FLUR) is the only FLU metabolite formed in the human liver. All human cancer cell lines were able to form FLUR. In addition, methylated FLUR was detected in breast cells MCF7 and intestinal SW480 cells. The accumulation of FLU and its reduction to FLUR markedly differed among cells. The extent of FLU reduction was in a good correlation with the detected expression level of carbonyl reductase 1. In most cases, FLU entered in a higher amount and was reduced to a lesser extent in proliferating (metastatic) cells than in differentiated (non-cancerous, non-metastatic) ones. These results support the promising potential of FLU in anti-cancer therapy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug Testing and Analysis
ISSN
1942-7603
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
7
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
1139-1146
UT code for WoS article
000439505100010
EID of the result in the Scopus database
2-s2.0-85044224272