engleski

The role of de novo expressed sirtuin 3 in triple negative human breast cancer cells upon oxidative stress

Hyperoxic treatment (inducer of reactive oxygen species, ROS) was shown to support some tumorigenic properties, but finally suppresses growth of certain mammary carcinoma cells. While estrogen receptor α cancers are more receptive to hormonal therapy, triple negative breast cancers (TNBC) are characterized by an aggressive behaviour and the lack of targeted therapeutic strategies. Sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has bifunctional role in cancer tumorigenesis depending on the tissue and cancer-type specific metabolic programs. Due to strikingly reduced Sirt3 level in many breast cancer cells, we hypothesized it would have tumor suppressive effect in TNBC cells. Therefore, we stably transfected MDA-MB-231 cells with Flag- tagged Sirt-3 or empty plasmid and exposed cell to hyperoxic treatment. We are checking the expression of the proteins involved in mitochondrial biogenesis, metabolic regulation and antioxidant defence. Furthermore, we are investigating growth rate, metabolic activity and mitochondrial function through cellular respiration and FACS analysis. The surprising finding that Sirt-3 markedly promoted metabolic activity of TNBC cells, but reduced their potential to form new colonies and induced the mitochondrial ROS production compared to control cells gave us a rationale for more detailed studies on Sirt3 and hyperoxia as an adjuvant tumor therapy in TNBC cells.

hyperoxia ; sirtuin 3 ; triple negative breast cancer ; MDA-MB-231 ; oxidative stress

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