Oxidative stress plays a key role in butyrate-mediated autophagy via Akt/mTOR pathway in hepatoma cells. (1st August 2017)

• Record Type: Journal Article
• Authors: Pant, Kishor; Saraya, Anoop; Venugopal, Senthil K.
• Is Part Of: Chemico-biological interactions. Volume 273(2017)
• Page Start: 99
• Page End: 106
• Publication Date: 2017-08-01
• Subjects: Butyrate -- ROS -- Autophagy -- Hepatocellular carcinoma; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.06.001
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Hepatocellular Carcinoma (HCC) is one of the most aggressive forms of cancer, responsible for a number of deaths in humans. Butyrate, one of the short chain fatty acids produced by the gut microbiota during anaerobic fermentation, was shown to be beneficial for inhibiting cancer growth. In this study, we showed that sodium butyrate induced autophagy via reactive oxygen species (ROS) in hepatoma cells. Butyrate (0–6 mM) incubation significantly increased intracellular ROS levels (45.2% compared to control), which in turn inhibited phosphorylation of akt and mTOR, leading to the upregulation of autophagic proteins, such as beclin 1, ATG 5, LC3-II, followed by the increased autophagosome formation (34.4% compared to control cells). Addition of a known antioxidant, N-acetyl cysteine (NAC), reversed these butyrate-induced ROS and autophagy. It was also found that butyrate-induced ROS enhanced MAPK activation, which was inhibited by NAC. In conclusion, our data showed that butyrate induced ROS, which in turn induced autophagy via inhibition of akt/mTOR pathway. Hence, butyrate could be considered as a potential candidate for HCC treatment. Highlights: Butyrate induced reactive oxygen species (ROS). ROS activated akt/mTOR/beclin 1/autophagosome formation. ROS also activated Erk 1/2, p38 MAP Kinase and Jnk 1/2. Butyrate-induced ROS induced autophagy.