engleski

Sirtuin 3 and hyperoxia: Allies in the fight against tumors

Mitochondria, as the major reactive oxygen species (ROS) producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. Oxidative stress and high levels of ROS cause DNA damage and genomic instability, which lead to changes in cell metabolism and ultimately loss of control of the cell cycle. These conditions support continuous growth and proliferation, the main characteristics of tumor cells. Although the role of pure oxygen (hyperoxia) as a promoter of malignant diseases has long been debated, today hyperoxia is used as a routine therapy to treat such diseases. Sirtuin-3 (Sirt-3) is a major mitochondrial NAD+-dependent deacetylase that plays critical role in activation of mitochondrial proteins involved in energy metabolism, ATP production and mitochondrial biogenesis which effectively keeps the cell in energetic homeostasis. In addition, Sirt-3 has a role as an oncogene, but also as a tumor suppressor in tumor cells, and it is not clear which factors lead to the change in the protein’s function. In this research we investigated the effect of Sirt-3 on the proliferation, survival, growth, metabolic activity, oxidant/antioxidant status, apoptosis and mitochondrial function of the MCF-7 breast cancer tumor cell line in normoxia and after treatment in hyperoxia. We confirmed that in normoxic conditions, Sirt-3 functions as an oncogene, and causes oxidative stress and other factors responsible for tumor growth. We also confirmed that in hyperoxic conditions, Sirt-3 functions as a tumor suppressor because it decreases the tumor cell characteristics usually present in breast cancer MCF-7 cells. With our research we have shown that Sirt-3 regulates numerous cell processes essential for the proliferation and metastasis of tumor cells, and that hyperoxia encourages the tumor suppressor activity of Sirt-3. These characteristics make Sirt-3 a potential therapeutic target in combination with hyperoxia to treat malignant diseases.

hyperoxia ; sirtuin 3 ; breast cancer ; mitochondria ; oxidative stress

nije evidentirano