N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression.

Autor: Andrade JK; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil., Souza MI; Department of Pharmaceutical Sciences, Federal University of Pernambuco, Pernambuco, Brazil., Gomes Filho MA; Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Pernambuco, Brazil., Silva DM; Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Pernambuco, Brazil., Barros AL; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil., Rodrigues MD; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil., Silva PB; Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil., Nascimento SC; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil., Aguiar JS; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil., Brondani DJ; Department of Pharmaceutical Sciences, Federal University of Pernambuco, Pernambuco, Brazil., Militão GC; Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil., Silva TG; Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil. Electronic address: teresinha.goncalves@pq.cnpq.br.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2016 Oct; Vol. 68 (5), pp. 1046-53. Date of Electronic Publication: 2016 Aug 06.
DOI: 10.1016/j.pharep.2016.06.004
Abstrakt: Background: Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells.
Methods: Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR.
Results: NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased.
Conclusion: The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.
(Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)
Databáze: MEDLINE
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