title: N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression.
abstract: 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.
  
  
  CONCLUSIONS
  The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Jeyce K F
authors: JK
authors: Andrade
authors: Department of Pharmaceutical Sciences, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Márcia I F
authors: MI
authors: Souza
authors: Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Pernambuco, Brazil.
authors: Manoel A
authors: MA
authors: Gomes Filho
authors: Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Pernambuco, Brazil.
authors: Diogo M F
authors: DM
authors: Silva
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil.
authors: André L S
authors: AL
authors: Barros
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Maria D
authors: MD
authors: Rodrigues
authors: Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Paulo B N
authors: PB
authors: Silva
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Silene C
authors: SC
authors: Nascimento
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Jaciana S
authors: JS
authors: Aguiar
authors: Department of Pharmaceutical Sciences, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Dalci J
authors: DJ
authors: Brondani
authors: Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil.
authors: Gardênia C G
authors: GC
authors: Militão
authors: Department of Antibiotics, Federal University of Pernambuco, Pernambuco, Brazil. Electronic address: teresinha.goncalves@pq.cnpq.br.
authors: Teresinha G
authors: TG
authors: Silva
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D009582:Nitrofurantoin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009582:Nitrofurantoin
keywords: Cytotoxicity; Flow cytometry; N-pentyl-nitrofurantoin; Nitroderivative