Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in HepG2 cells

被引:33
作者
Krause, Gabriele Catyana [1 ]
Lima, Kelly Goulart [1 ]
Dias, Henrique Bregolin [1 ]
Goncalves da Silva, Elisa Feller [1 ]
Haute, Gabriela Viegas [1 ]
Basso, Bruno Souza [1 ]
Gassen, Rodrigo Benedetti [2 ]
Marczak, Elisa Simon [2 ]
Bach Nunes, Rafaela Sole [1 ]
de Oliveira, Jarbas Rodrigues [1 ,2 ]
机构
[1] Pontificia Univ Catolica Rio Grande do Sul PUCRS, Lab Pesquisa Biofis Celular & Inflamacao, Av Ipiranga 6681,Predio 12,Bloco C, BR-90619900 Porto Alegre, RS, Brazil
[2] Pontificia Univ Catolica Rio Grande do Sul PUCRS, Lab Imunol Clin & Expt, Inst Pesquisas Biomed, Porto Alegre, RS, Brazil
关键词
Liraglutide; HepG2; Hepatocellular carcinoma; Autophagy; Senescence; TGF-beta; 1; PANCREATIC-CANCER CELLS; INHIBITS GROWTH; HEPATOCELLULAR-CARCINOMA; AUGMENTS APOPTOSIS; EXOCRINE PANCREAS; NO EVIDENCE; RECEPTOR; ACTIVATION; MICE; ENDOCRINE;
D O I
10.1016/j.ejphar.2017.05.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been reported that glucagon-like peptide-1 (GLP-1) agents have been associated with both the increased risk of cancer and inhibition of tumor growth and metastases. The aim of this study is to evaluate the effect of liraglutide on hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism related to decreased cell proliferation. Nuclear staining and morphometric analysis were also used to verify the process that was taking place after treatment with liraglutide, and in order to better understand the mechanism, TGF-beta 1 was performed. HepG2 cells decreased proliferation after liraglutide treatment without altering oxidative stress levels. Liraglutide was able to induce autophagy and senescence through the increase of TGF-beta 1 which possibly explains the growth decrease. We have demonstrated that liraglutide has an antiproliferative effect in HepG2 cells inducing autophagy and senescence by the increase of TGF-beta 1.
引用
收藏
页码:32 / 41
页数:10
相关论文
共 45 条
[1]   The role of glutathione in cancer [J].
Balendiran, GK ;
Dabur, R ;
Fraser, D .
CELL BIOCHEMISTRY AND FUNCTION, 2004, 22 (06) :343-352
[2]  
BEUTLER E, 1963, J LAB CLIN MED, V61, P882
[3]   The Restriction Point of the Cell Cycle [J].
Blagosklonny, Mikhail V. ;
Pardee, Arthur B. .
CELL CYCLE, 2002, 1 (02) :103-110
[4]   Reducing mammary cancer risk through premature stem cell senescence [J].
Boulanger, CA ;
Smith, GH .
ONCOGENE, 2001, 20 (18) :2264-2272
[5]   The glucagon-like peptides - Pleiotropic regulators of nutrient homeostasis [J].
Brubaker, Patricia L. .
VIP, PACAP, AND RELATED PEPTIDES: FROM GENE TO THERAPY, 2006, 1070 :10-26
[6]   Marked Expansion of Exocrine and Endocrine Pancreas With Incretin Therapy in Humans With Increased Exocrine Pancreas Dysplasia and the Potential for Glucagon-Producing Neuroendocrine Tumors [J].
Butler, Alexandra E. ;
Campbell-Thompson, Martha ;
Gurlo, Tatyana ;
Dawson, David W. ;
Atkinson, Mark ;
Butler, Peter C. .
DIABETES, 2013, 62 (07) :2595-2604
[7]   Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation [J].
Chang, Tien-Jyun ;
Tseng, Hsing-Chi ;
Liu, Meng-Wei ;
Chang, Yi-Cheng ;
Hsieh, Meng-Lun ;
Chuang, Lee-Ming .
SCIENTIFIC REPORTS, 2016, 6
[8]   REGULATION OF CELLULAR GLUTATHIONE [J].
DENEKE, SM ;
FANBURG, BL .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (04) :L163-L173
[9]   MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS [J].
DONEHOWER, LA ;
HARVEY, M ;
SLAGLE, BL ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
BUTEL, JS ;
BRADLEY, A .
NATURE, 1992, 356 (6366) :215-221
[10]   Liraglutide [J].
Drucker, Daniel J. ;
Dritselis, Argyris ;
Kirkpatrick, Peter .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (04) :267-268