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In vivo inhibition of tumor progression by 5 hydroxy-1,4-naphthoquinone (juglone) and 2-(4-hydroxyanilino)-1,4-naphthoquinone (Q7) in combination with ascorbate.
Ourique, Fabiana; Kviecinski, Maicon R; Zirbel, Guilherme; Castro, Luiza S E P W; Gomes Castro, Allisson Jhonatan; Mena Barreto Silva, Fátima Regina; Valderrama, Jaime A; Rios, David; Benites, Julio; Calderon, Pedro Buc; Pedrosa, Rozangela Curi.
Afiliação
  • Ourique F; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • Kviecinski MR; Postgraduate Programe of Health Science, Universidade do Sul de Santa Catarina (UNISUL), Palhoça, SC, Brazil.
  • Zirbel G; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • Castro LSEPW; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • Gomes Castro AJ; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • Mena Barreto Silva FR; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • Valderrama JA; Department of Chemical and Pharmaceutical Sciences, Universidad Arturo Prat, Iquique, Chile.
  • Rios D; Department of Chemical and Pharmaceutical Sciences, Universidad Arturo Prat, Iquique, Chile.
  • Benites J; Department of Chemical and Pharmaceutical Sciences, Universidad Arturo Prat, Iquique, Chile.
  • Calderon PB; Toxicology and Cancer Biology Research Group (GTOX), Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
  • Pedrosa RC; Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil. Electronic address: rozangelapedrosa@gmail.com.
Biochem Biophys Res Commun ; 477(4): 640-646, 2016 09 02.
Article em En | MEDLINE | ID: mdl-27346131
ABSTRACT
The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with (14)C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Ehrlich / Protocolos de Quimioterapia Combinada Antineoplásica Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Ehrlich / Protocolos de Quimioterapia Combinada Antineoplásica Idioma: En Ano de publicação: 2016 Tipo de documento: Article