Regulations of expressions of rat/human sulfotransferases by anticancer drug, nolatrexed, and micronutrients.
Animals
Antimetabolites, Antineoplastic
/ administration & dosage
Arylsulfotransferase
/ drug effects
Blotting, Western
Cell Cycle
Dose-Response Relationship, Drug
Female
Folic Acid
/ administration & dosage
Hep G2 Cells
Humans
Leucovorin
/ administration & dosage
Male
Methotrexate
/ administration & dosage
Micronutrients
/ administration & dosage
Quinazolines
/ administration & dosage
RNA, Messenger
/ biosynthesis
Rats
Rats, Sprague-Dawley
Sex Factors
Sulfotransferases
/ drug effects
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
14
8
2021
medline:
5
3
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
Cancer is related to the cellular proliferative state. Increase in cell-cycle regulatory function augments cellular folate pool. This pathway is therapeutically targeted. A number of drugs influences this metabolism, that is, folic acid, folinic acid, nolatrexed, and methotrexate. Our previous study showed methotrexate influences on rat/human sulfotransferases. Present study explains the effect of nolatrexed (widely used in different cancers) and some micronutrients on the expressions of rat/human sulfotransferases. Female Sprague-Dawley rats were treated with nolatrexed (01-100 mg/kg) and rats of both sexes were treated to folic acid (100, 200, or 400 mg/kg) for 2-weeks and their aryl sulfotransferase-IV (AST-IV; β-napthol sulfation) and sulfotransferase (STa; DHEA sulfation) activities, protein expression (western blot) and mRNA expression (RT-PCR) were tested. In human-cultured hepatocarcinoma (HepG2) cells nolatrexed (1 nM-1.2 mM) or folinic acid (10 nM-10 μM) were applied for 10 days. Folic acid (0-10 μM) was treated to HepG2 cells. PPST (phenol catalyzing), MPST (dopamine and monoamine), DHEAST (dehydroepiandrosterone and DHEA), and EST (estradiol sulfating) protein expressions (western-blot) were tested in HepG2 cells. Present results suggest that nolatrexed significantly increased sulfotransferases expressions in rat (protein, STa, F = 4.87, P < 0.05/mRNA, AST-IV, F = 6.702, P < 0.014; Student's t test, P < 0.01-0.05) and HepG2 cells. Folic acid increased sulfotransferases activity/protein in gender-dependant manner. Both folic and folinic acid increased several human sulfotransferases isoforms with varied level of significance (least or no increase at highest dose) in HepG2 cells pointing its dose-dependent multiphasic responses. The clinical importance of this study may be furthered in the verification of sulfation metabolism of several exogenous/endogenous molecules, drug-drug interaction and their influences on cancer pathophysiological processes. Further studies are necessary.
Identifiants
pubmed: 34387600
doi: 10.1097/CAD.0000000000001155
pii: 00001813-202201000-00068
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Micronutrients
0
Quinazolines
0
RNA, Messenger
0
Folic Acid
935E97BOY8
Sulfotransferases
EC 2.8.2.-
Arylsulfotransferase
EC 2.8.2.1
nolatrexed
K75ZUN743Q
Leucovorin
Q573I9DVLP
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e525-e533Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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