Oxidative Stress Pathway Mechanisms Induced by Four Individual Heavy Metals (As, Hg, Cd and Pb) and Their Quaternary on MCF-7 Breast Cancer Cells

Egbe Egiebor

Department of Public Health, University of Illinois at Springfield, Springfield, Illinois, 62703, USA.

Adam Tulu

Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland, 21853, USA

Nadia Abou-Zeid

Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland, 21853, USA

Ozuem F. Oseji

Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland, 21853, USA

Ali B. Ishaque *

Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland, 21853, USA

*Author to whom correspondence should be addressed.


Abstract

Cell death induced by the production of reactive oxygen species (ROS) has largely been associated with the activation of oxidative stress pathway; however, the direct mechanism(s) involved are unknown. This study evaluates the oxidative stress pathways by which four heavy metals (As, Hg, Cd and Pb) administered singly and as a quaternary mixture induce cytotoxic effects on MCF-7 breast cancer cells, in the presence and absence of cellular antioxidant, glutathione (GSH). Cells were exposed to 21.7 µg/ml of the individual metals and the mixture and assayed after 5 hr. Cellular levels of nonspecific ROS, superoxide anion (O2•), mitochondria membrane potential (MMP), and GSH were assayed using flow cytometry-FACScalibur equipped with cell quest pro for data collection. Results showed that, in the presence of cellular GSH, As and Pb induced cytotoxicity by reducing the MMP while Cd, and Hg were cytotoxic by the production of mostly superoxide anions and nonspecific ROS. The mixture exhibited cytotoxicity by decreasing the cellular MMP as well as producing ROS and O2•. When the synthesis of cellular glutathione was inhibited, all five treatments damaged the mitochondria membrane and depleted basal GSH. In addition to depleting the basal GSH and causing damage to the mitochondria membrane, Cd, As, and Pb also elicited the production of ROS.

Keywords: Heavy metals, cytotoxicity, glutathione, reactive oxygen species, superoxide anion, MCF-7 cells.


How to Cite

Egiebor, Egbe, Adam Tulu, Nadia Abou-Zeid, Ozuem F. Oseji, and Ali B. Ishaque. 2016. “Oxidative Stress Pathway Mechanisms Induced by Four Individual Heavy Metals (As, Hg, Cd and Pb) and Their Quaternary on MCF-7 Breast Cancer Cells”. Journal of Advances in Medicine and Medical Research 17 (7):1-11. https://doi.org/10.9734/BJMMR/2016/27687.

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