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Title: 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

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 {sup 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 withmore » 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. - Highlights: • Ascorbate potentiates the inhibition caused by juglone and Q7on tumor progress in vivo. • Juglone and Q7 with ascorbate caused widespread oxidative stress in tumor tissue. • Treatments inhibited HIF-1 and GLUT1 expression causing reduced glucose uptake. • Treatments induced cell cycle arrest and apoptosis in tumor in vivo.« less

Authors:
 [1];  [2]; ; ; ;  [1]; ; ;  [3];  [4];  [1]
  1. Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC (Brazil)
  2. Postgraduate Programe of Health Science, Universidade do Sul de Santa Catarina (UNISUL), Palhoça, SC (Brazil)
  3. Department of Chemical and Pharmaceutical Sciences, Universidad Arturo Prat, Iquique (Chile)
  4. Toxicology and Cancer Biology Research Group (GTOX), Louvain Drug Research Institute, Université Catholique de Louvain, Brussels (Belgium)
Publication Date:
OSTI Identifier:
22606181
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 477; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACRIDINE ORANGE; ADP; ANIMAL TISSUES; ANTIOXIDANTS; APOPTOSIS; ASCITES; BORON CHLORIDES; BROMIDES; CARBON 14; CARBONYLATION; CATALASE; CELL CULTURES; CELL CYCLE; EHRLICH ASCITES TUMOR; GLUCOSE; GLUTATHIONE; IN VIVO; INHIBITION; LIQUIDS; MICE; OXIDATION; SUPEROXIDE DISMUTASE; TUMOR CELLS; UPTAKE

Citation Formats

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, and Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com. 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. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.06.113.
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, E-mail: rozangelapedrosa@gmail.com. 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. United States. doi:10.1016/J.BBRC.2016.06.113.
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, and Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com. Fri . "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". United States. doi:10.1016/J.BBRC.2016.06.113.
@article{osti_22606181,
title = {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},
author = {Ourique, Fabiana and Kviecinski, Maicon R. and Zirbel, Guilherme and Castro, Luiza S.E.P.W. and Gomes Castro, Allisson Jhonatan and Mena Barreto Silva, Fátima Regina and Valderrama, Jaime A. and Rios, David and Benites, Julio and Calderon, Pedro Buc and Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com},
abstractNote = {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 {sup 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. - Highlights: • Ascorbate potentiates the inhibition caused by juglone and Q7on tumor progress in vivo. • Juglone and Q7 with ascorbate caused widespread oxidative stress in tumor tissue. • Treatments inhibited HIF-1 and GLUT1 expression causing reduced glucose uptake. • Treatments induced cell cycle arrest and apoptosis in tumor in vivo.},
doi = {10.1016/J.BBRC.2016.06.113},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 477,
place = {United States},
year = {Fri Sep 02 00:00:00 EDT 2016},
month = {Fri Sep 02 00:00:00 EDT 2016}
}