Boron treatment induces metabolic reprogramming in hepatocellular carcinoma through SIRT3 activation

Sirtuins are members of NAD+-dependent deacetylases and ADP ribosyltransferases, activated under stress conditions such as calorie restriction and starvation. Boron, mostly found in the form of boric acid (BA) or sodium borate (NaB), is known to bind NAD+. In this study, particularly the effect of NaB on hepatoma cell line, HEP3B was investigated by analyzing the proteins harvested from NaB-treated and serum-starved HEP3B cells. It was discovered that treatment of cells with NaB (15 μg/ml) led to a decrease in the overall proteome acetylation specifically in mitochondria, in the synthesis rate of oxidative phosphorylation (OXPHOS) machinery subunits, in the amount of cellular reactive oxygen species (ROS), and in the proliferation rate of HEP3B cells. On the other hand, the cellular ratio of NAD+/NADH and deacetylase activity of mitochondrial sirtuin, SIRT3 showed an increase. The results of this study suggest a link between boron treatment and activation of SIRT3 by means of affecting the cellular metabolism. In the scope of this study, it is expected to pave the way for new findings uncovering the metabolic changes in HEP3B cells related to SIRT3 activity upon NaB treatment.