title: DNA damage and inhibition of akt pathway in mcf-7 cells and ehrlich tumor in mice treated with 1,4-naphthoquinones in combination with ascorbate.
abstract: The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells.
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Fabiana
authors: F
authors: Ourique
authors: Programa de Pós-Graduação em Ciências da Saúde da Universidade do Sul de Santa Catarina (UNISUL), SC, Brazil.
authors: Maicon R
authors: MR
authors: Kviecinski
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Karina B
authors: KB
authors: Felipe
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: João Francisco Gomes
authors: JF
authors: Correia
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Mirelle S
authors: MS
authors: Farias
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Luiza S E P W
authors: LS
authors: Castro
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Valdelúcia M A S
authors: VM
authors: Grinevicius
authors: Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, 2120 Avenida Arturo Prat, Iquique, Chile.
authors: Jaime
authors: J
authors: Valderrama
authors: Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, 2120 Avenida Arturo Prat, Iquique, Chile.
authors: David
authors: D
authors: Rios
authors: Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, 2120 Avenida Arturo Prat, Iquique, Chile.
authors: Julio
authors: J
authors: Benites
authors: Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, 73 Avenue E. Mounier, GTOX 7309, 1200 Brussels, Belgium.
authors: Pedro Buc
authors: PB
authors: Calderon
authors: Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Rozangela Curi
authors: RC
authors: Pedrosa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C468783:H2AX protein, human; D006657:Histones; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D001205:Ascorbic Acid; C035342:1,4-naphthoquinone; C005134:juglone