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

Abstract

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-β1 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-β1 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-β1.

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

“…Autophagy is a catabolic process in which cells are subjected to stress such as hypoxia, starvation, and lack of nutrients (15). Autophagy acts as a 'double-edged sword' in tumorigenesis and development (16,17). On one hand, autophagy inhibits the occurrence and development of tumors by degrading abnormal components in cells or inducing non-apoptotic pathway death.…”

Exenatide induces autophagy and prevents the cell regrowth in HepG2 cells

“…Moreover, experimental studies have shown that exendin-4 could inhibit and attenuates tumor growth (Honors and Kinzig, 2014[13]; Nomiyama et al, 2014[19]). Other studies revealed that GLP-1 analog liraglutide inhibits the growth of pancreatic cancer in animal models and hepatocellular carcinoma in HepG2 cell line (Zhao et al, 2014[29]; Krause et al, 2017[14]). These results corroborate our findings that exenatide decrease HepG2 cells viability after 48 h of treatment.…”

“…Knowing that liraglutide is capable of inducing senescence in HepG2 cells (Krause et al, 2017[14]), we have tested this effect for exenatide. Senescence and apoptosis are two mechanisms that may be responsible for the proliferation decrease, as the first is characterized by an irreversible cell cycle arrest (Childs et al, 2014[5]) and the second by a programmed cell death with nuclear fragmentation (He et al, 2009[11]).…”

“…Exenatide (Byetta, Baxter Pharmaceutical Solutions, USA) and liraglutide (Victoza, Novo Nordisk A/S, Denmark) were used at a final concentration of 15 µM (Krause et al, 2017[14]). HepG2 cells were incubated and the analyses were performed 48 h after treatment.…”

“…Thus, considering that we have previously shown that liraglutide, a GLP-1 analog, presents chemotherapeutic effects for cancer by inducing autophagy and senescence in hepatocarcinoma cells (Krause et al, 2017[14]), the aim of this study was to compare the antiproliferative effects of exenatide and liraglutide.…”