Abstract
BackgroundObesity is associated with oxidative stress, a major factor in carcinogenesis, and with high leptin concentration. The aim of this study was to determine the effects of leptin on the antioxidant response in three human mammary epithelial cells each presenting a different neoplastic status: healthy human mammary epithelial cells (HMEC), oestrogen-receptor positive MCF-7 cells and triple-negative MDA-MB-231 cells.MethodsThis in vitro kinetic study characterized the cell antioxidant response after 1, 6 and 24 h in the presence of leptin (10 or 100 ng/ml).The antioxidant response was defined in terms of cell glutathione content, gene expression and catalytic activity of antioxidant enzymes (i.e. glutathione peroxidase 1 (Gpx1), glutathione reductase (GR), glutathione S transferase (GST), heme-oxygenase 1 (HO-1) and cyclooxygenase-2 (COX-2)). Oxidative stress occurrence was assessed by lipid hydro peroxide (HPLIP) and isoprostane concentrations in culture media at 24 h.ResultsAt both concentrations used, leptin induced ROS production in all cell models, contributing to various antioxidant responses linked to neoplastic cell status. HMEC developed a highly inducible antioxidant response based on antioxidant enzyme activation and an increase in cell GSH content at 10 ng/ml of leptin. However, at 100 ng/ml of leptin, activation of antioxidant response was lower. Conversely, in tumour cells, MCF-7 and MDA-MB-231, leptin did not induce an efficient antioxidant response, at either concentration, resulting in an increase of lipid peroxidation products.ConclusionsLeptin can modulate the oxidative status of mammary epithelial cells differently according to their neoplastic state. These novel results shed light on oxidative status changes in mammary cells in the presence of leptin.
Highlights
Obesity is associated with oxidative stress, a major factor in carcinogenesis, and with high leptin concentration
An adipokine upregulated during obesity, has been widely studied in carcinogenesis because of its many signalling pathways [4] involved in critical steps of pathogenesis such as cell proliferation [5, 6], inflammatory response [7] and modulation of the tumour environment [8]
The determination of cytosolic reactive oxygen species (ROS) production, of glutathione and protein-thiol contents and of antioxidant catalytic activities characterized the oxidative status of our different mammary epithelial cell models under basal condition
Summary
Obesity is associated with oxidative stress, a major factor in carcinogenesis, and with high leptin concentration. Because oxidative stress can be induced by obesity [16] and has a known role in carcinogenesis [12] we Mahbouli et al BMC Cancer (2018) 18:1264 set out to study the oxidative status of different mammary epithelial cells. The mRNA expression and catalytic activity of cyclooxygenase 2 (COX-2) were determined, as this enzyme is a well-known prognostic factor in early breast cancer [34] and makes a link between oxidative stress and inflammation [31]. These markers characterize the antioxidant response to oxidative stress: high GSH content or antioxidant enzyme activities, induced by oxidative stress, define a protective state. Low GSH content or antioxidant enzyme activities, associated with a loss of inducibility to oxidative stress, define an aggressive state [24, 35]
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