De novo expression of transfected sirtuin 3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment

Pinterić, Marija; Podgorski, Iva I.; Sobočanec, Sandra; Popović Hadžija, Marijana; Paradžik, Mladen; Dekanić, Ana; Marinović, Maja; Halasz, Mirna; Belužić, Robert; Davidović, Grazia; Ambriović Ristov, Andreja; Balog, Tihomir (2018) De novo expression of transfected sirtuin 3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment. Free Radical Research, 52 (6). pp. 672-684. ISSN 1071-5762

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Abstract

Sirtuin 3 (Sirt3) has a promising role in cancer tumourigenesis and treatment, but there have been controversies about its role as oncogene or tumour suppressor in different types of cancer. Changes in its expression are associated with the excessive production of reactive oxygen species (ROS), thus contributing to mitochondrial dysfunction and age-related pathologies. Hyperoxic treatment (i.e. generator of ROS) was shown to support some tumourigenic properties, but finally suppresses growth of certain mammary carcinoma cells. Due to strikingly reduced Sirt3 level in many breast cancer cell lines, we aimed to clarify the effect of de novo Sirt3 expression upon hyperoxic treatment in the human MCF-7 breast cancer cells. De novo expression of Sirt3 decreased metabolic activity and cellular growth of MCF-7 cells, reduced expression of proangiogenic and epithelial mesenchymal transition genes, induced metabolic switch from glycolysis to oxidative phosphorylation, and decreased abundance of senescent cells. These effects were enhanced upon hyperoxic treatment: induction of DNA damage and upregulation of p53, with an increase of ROS levels followed by mitochondrial and antioxidant dysfunction, resulted in additional reduction of metabolic activity and inhibition of cellular growth and survival. 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 indicates that these factors, individually and in combination, should be further explored in vitro and particularly in vivo, as an adjuvant tumour therapy in breast cancer malignancies.

Item Type:	Article
Uncontrolled Keywords:	Hyperoxia; MCF-7; ROS; mitochondrial function; sirtuin 3
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom masti-SuMERA Tihomir Balog IP-2014-09-4533 HRZZ
Depositing User:	Iva Škrinjar
Date Deposited:	19 Nov 2019 13:38
URI:	http://fulir.irb.hr/id/eprint/5085
DOI:	10.1080/10715762.2018.1462495

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