Oxidative stress and breast cancer biomarkers : the case of the cytochrome P450 2E1

Singh, S; Rajendran, R; Kuroda, K; Isogai, E; Krstic-Demonacos, M; Demonacos, C

Abstract

Aim: The aim of the study is to investigate the impact of the cytochrome P450 2E1, which is the most efficient CYP450 family
member in generating reactive oxygen species (ROS), on cellular energy metabolism of breast cancer cells and therefore the
effects of CYP2E1 on breast carcinogenesis. Methods: The estrogen receptor positive MCF-7 and the triple negative MDAMB-
231 breast cancer cells were used as experimental system to estimate ROS generation in these cells overexpressing CYP2E1
and treated with the glycolytic inhibitors 3-bromopyruvate or 2-deoxyglucose in the presence or absence of the CYP2E1 inhibitor
chlormethiazole. Adenosine triphosphate (ATP) assay was used to measure ATP production and lactate assay to quantify the efflux
of lactic acid in breast cancer cells treated with the CYP2E1 inhibitor chlormethiazole, the mitochondrial membrane potential
and cell viability assays were employed to assess the pathway of cellular energy production and cellular death respectively after
treatment of MCF-7 and MDA-MB-231 with the CYP2E1 activator acetaminophen or the CYP2E1 inhibitor chlormethiazole.
Results: T he r esults i ndicated i ncreased ROS generation i n b reast c ancer c ells overexpressing C YP2E1. ROS generation was
differentially regulated in breast cancer cells upon treatment with the CYP2E1 inhibitor chlormethiazole. Chlormethiazole
treated MCF-7 cells exhibited reduced lactate efflux implying that CYP2E1 directly or indirectly regulates the glycolytic rate
in these cells. Furthermore the mitochondrial membrane potential of both MCF-7 and MDA-MB-231 cells was differentially
affected by the CYP2E1 activator acetaminophen versus the CYP2E1 inhibitor chlormethiazole providing additional support for
the involvement of CYP2E1 in energy metabolic pathways in breast cancer. Conclusion: Results presented in this study provide
evidence to suggest that CYP2E1 regulates cellular energy metabolism of breast cancer cells in a manner dependent on cell type
and potentially on the clinical staging of the disease therefore CYP2E1 is a possible breast cancer biomarker.

Citation

Singh, S., Rajendran, R., Kuroda, K., Isogai, E., Krstic-Demonacos, M., & Demonacos, C. (2016). Oxidative stress and breast cancer biomarkers : the case of the cytochrome P450 2E1. Journal of Cancer Metastasis and Treatment, 2, 268-276. https://doi.org/10.20517/2394-4722.2016.42

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2016
• Publication Date: Jul 29, 2016
• Deposit Date: Sep 21, 2016
• Publicly Available Date: Sep 21, 2016
• Journal: Journal of Cancer Metastasis and Treatment
• Print ISSN: 2394-4722
• Electronic ISSN: 2454-2857
• Volume: 2
• Pages: 268-276
• DOI: https://doi.org/10.20517/2394-4722.2016.42
• Publisher URL: http://dx.doi.org/10.20517/2394-4722.2016.42
• Related Public URLs: http://www.jcmtjournal.com
• Additional Information: Funders : Manchester Pharmacy School, University of Manchester