engleski

De novo expression of transfected Sirt3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment

Sirtuin 3 (Sirt3) has a promising role in cancer tumorigenesis and treatment, but there have been controversies about its role as tumor suppressor or promoter in different types of cancer. Hyperoxic treatment (i.e. generator of reactive oxygen species (ROS)) was shown to suppress growth of certain mammary carcinoma cells. Due to strikingly reduced Sirt3 level in many breast cancer cells and changes in its expression associated with the production of ROS, we studied the effect of de novo Sirt3 expression in the human MCF-7 breast cancer cells upon 44 hours long hyperoxic treatment. Effects of Sirt3 were enhanced upon hyperoxic treatment: decreased metabolic activity and cellular growth, reduced expression of pro-angiogenic genes, induced metabolic switch from glycolysis to OXPHOS, decreased cellular senescence, induced DNA damage and upregulated p53, increased ROS levels followed by mitochondrial and antioxidant dysfunction. The mitigation of tumorigenic properties and enhancement of the susceptibility of the MCF-7 breast cancer cells to the hyperoxic treatment upon de novo Sirt3 expression, gives rationale for further in vitro and particularly in vivo studies which would combine these two factors as an adjuvant tumor therapy in breast cancer malignancies.

Hyperoxia ; MCF-7 ; ROS ; mitochondrial function ; sirtuin 3

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