Breast Cancer Cell Lines, HER2/Neu Phenotype, and a Higher Propensity to Reactive Oxygen Species Production

The reactive oxygen species (ROS) generated in the biological systems play an important role in pathological conditions and specific normal cellular processes, such as signaling pathways and drug sensitivity.

Intracellular ROS was determined using (2'-7'dichlorofluorescin diacetate) DCFH-DA fluorimetric probe, malondialdehyde as lipid peroxidation index detected by the Thiobarbituric acid reactive substances method. Cells' protein carbonyl contents were assessed with 2,4-Dinitrophenylhydrazine (DNPH) derivatization spectrophotometrically at 360-385 nm.

The oxidative stress induces ROS (p˂0.05), MDA (Malondialdehyde) (p˂0.05), and protein carbonylation (p˂0.01) was significantly higher in HER2- positive BT-474, SK-BR-3, and MDA-MB-453 compared to the HER2-negative MDA-MB-231 and MCF-7 cell lines.

We hypothesized that increased oxidative stress in HER2-positive cell lines is due to the oncogenic function of the HER2 and PI3K/Akt signaling activation, resulting in glycolysis induction. It is assumed that HER2-positive cell lines with high ROS levels are more vulnerable to further damage by increased ROS levels induced by pro-oxidant anticancer agents.