TY - JOUR
T1 - Oxidative stress plays a key role in butyrate-mediated autophagy via Akt/mTOR pathway in hepatoma cells
AU - Pant, Kishor
AU - Saraya, Anoop
AU - Venugopal, Senthil K.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Autophagy
KW - Butyrate
KW - Hepatocellular carcinoma
KW - ROS
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UR - http://www.scopus.com/inward/citedby.url?scp=85020446036&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2017.06.001
DO - 10.1016/j.cbi.2017.06.001
M3 - Article
C2 - 28600122
AN - SCOPUS:85020446036
SN - 0009-2797
VL - 273
SP - 99
EP - 106
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -