Fructose-1,6-bisphosphate decreases IL-8 levels and increases the activity of pro-apoptotic proteins in HepG2 cells

被引:12
作者
Krause, Gabriele Catyana [1 ]
Lima, Kelly Goulart [1 ]
Haute, Gabriela Viegas [1 ]
Schuster, Aline Daniele [1 ]
Dias, Henrique Bregolin [1 ]
Mesquita, Fernanda Cristina [1 ]
Pedrazza, Leonardo [1 ]
Marczak, Elisa Simon [2 ]
Basso, Bruno Souza [1 ]
Velasque, Anderson Catarina [1 ]
Martha, Bianca Andrade [1 ]
Nunes, Fernanda Bordignon [1 ,3 ]
Fagundes Donadio, Marcio Vinicius [1 ]
de Oliveira, Jarbas Rodrigues [1 ,2 ,3 ]
机构
[1] Pontificia Univ Catolica Rio Grande do Sul, Lab Pesquisa Biofis Celular & Inflamacao, Porto Alegre, RS, Brazil
[2] Pontificia Univ Catolica Rio Grande do Sul, Inst Pesquisas Biomed, Lab Imunol Clin & Expt, Porto Alegre, RS, Brazil
[3] UFCSPA, Porto Alegre, RS, Brazil
关键词
Hepatocellular carcinoma; HepG2; Fructose-1,6-bisphosphate; Inflammation; IL-8; Bcl-2; INTERLEUKIN-8; CANCER; GALACTOSAMINE; METABOLISM; ACTIVATION; CARCINOMA; HEPATITIS;
D O I
10.1016/j.biopha.2017.01.178
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor that affects the world population. Liver cancer inevitably causes great harms and its treatment is extremely difficult. Its development is related to the existence of chronic liver injury, such as in cirrhosis. Cancer is a disease related to the process of inflammation so, research with anti-inflammatory agents has been performed for the development of anti-tumor drugs. Fructose-1,6-bisphosphate (FBP), a metabolite of the glycolytic route, has shown anti-inflammatory actions. The purpose of this study is to investigate the effect of FBP on HepG2 cells growth and inflammatory parameters. Results showed that FBP decreased the proliferation of HepG2 cells through trypan blue assay, without causing necrosis, shown by the intracellular release of LDH. By flow cytometry, we observed a significant IL-8 decrease which is closely related to the tumoral progression and chemotherapeutic resistance, especially in HCC. Then, we found, by RT-PCR, a high expression level of pro-apoptotic protein, such as Bax and p53, and decreased the expression levels of anti-apoptotic proteins, like Bcl-2 suggesting apoptosis. Finally, our results showed that FBP can be a potential therapeutic agent to slow the progress of HCC. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:358 / 365
页数:8
相关论文
共 42 条
[1]   Phase II study of sorafenib in patients with advanced hepatocellular carcinoma [J].
Abou-Alfa, Ghassan K. ;
Schwartz, Lawrence ;
Ricci, Sergio ;
Amadori, Dino ;
Santoro, Armando ;
Figer, Arie ;
De Greve, Jacques ;
Douillard, Jean-Yves ;
Lathia, Chetan ;
Schwartz, Brian ;
Taylor, Ian ;
Moscovici, Marius ;
Saltz, Leonard B. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (26) :4293-4300
[2]  
Akiba J, 2001, INT J ONCOL, V18, P257
[3]   Fructose 1,6 biphosphate administration to rats prevents metabolic acidosis and oxidative stress induced by deep hypothermia and rewarming [J].
Alva, Norma ;
Carbonell, Teresa ;
Roig, Teresa ;
Bermudez, Jordi ;
Palomeque, Jesus .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2011, 659 (2-3) :259-264
[4]   Effect of Fructose-1,6-bisphosphate on the Nephrotoxicity Induced by Cisplatin in Rats [J].
Azambuja, Alan Arrieira ;
Lunardelli, Adroaldo ;
Nunes, Fernanda Bordignon ;
Gaspareto, Patrick Barcelos ;
Fagundes Donadio, Marcio Vinicius ;
Poli de Figueiredo, Carlos Eduardo ;
de Oliveira, Jarbas Rodrigues .
INFLAMMATION, 2011, 34 (01) :67-71
[5]  
Bai JX, 2001, BIOL SIGNAL RECEPT, V10, P189
[6]   Fructose 1,6-bisphosphate reduced TNF-α-induced apoptosis in galactosamine sensitized rat hepatocytes through activation of nitric oxide and cGMP production [J].
Calafell, Roser ;
Boada, Jordi ;
Santidrian, Antonio F. ;
Gil, Joan ;
Roig, Teresa ;
Perales, Jose C. ;
Bermudez, Jordi .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 610 (1-3) :128-133
[7]   Fructose 1,6-bisphosphate prevented endotoxemia, macrophage activation, and liver injury induced by D-galactosamine in rats [J].
Cuesta, E ;
Boada, J ;
Calafell, R ;
Perales, JC ;
Roig, T ;
Bermudez, J .
CRITICAL CARE MEDICINE, 2006, 34 (03) :807-814
[8]   OXYGEN RADICAL SCAVENGERS SELECTIVELY INHIBIT INTERLEUKIN-8 PRODUCTION IN HUMAN WHOLE-BLOOD [J].
DEFORGE, LE ;
FANTONE, JC ;
KENNEY, JS ;
REMICK, DG .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (05) :2123-2129
[9]  
DEFORGE LE, 1993, J BIOL CHEM, V268, P25568
[10]   EFFECT OF GALACTOSAMINE ON HEPATIC CARBOHYDRATE-METABOLISM - PROTECTIVE ROLE OF FRUCTOSE-1,6-BISPHOSPHATE [J].
DEOLIVEIRA, JR ;
ROSA, JL ;
AMBROSIO, S ;
BARTRONS, R .
HEPATOLOGY, 1992, 15 (06) :1147-1153