Copper enriches efficacy of Dp44mT in breast cancer cells

Authors: UFUK ÖZER

Abstract: Neoplastic cells need essential metals, such as iron and copper, for cellular functions and rapid growth. Metal chelation and changes in their redox cycle in favor of oxidative stress may be critical for making these cells vulnerable to cell death. The HER2-overexpressing breast cancer cell line, MCF7-HER2, and its vehicle control, MCF7-vec cells, were treated with CuCl₂, FeSO₄, and Dp44mT. Reactive oxygen species (ROS) production in response to these chemicals was detected with flow cytometry, and cell viability was measured by MTT assay in the cells. ROS levels were relatively increased by Dp44mT in the cells, and this was reversed by a combination of iron, while a copper combination further induced ROS. Parallel changes were observed in the inhibition of cell growth by Dp44mT, and NAC partially rescued the inhibition. Additionally, copper decreased the CSC population by half relative to the control in MCF7-HER2 cells. Copper supplement enriches ROS production mediated by Dp44mT in MCF7 cells. However, iron addition recovers Dp44mT-depleted iron levels, yet has no effect on ROS generation. Copper treatment also decreases the proportion of CSCs. In this manner, Dp44mT depletes iron and binds copper to form a redox active complex, which leads to oxidative stress. This dual cytotoxic case is significant for the survival of cancer cells.

Keywords: Copper, iron, Dp44mT, metal chelation, reactive oxygen species, HER2

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