Ferroptosis Induction in Breast Cancer Cell Line MDA-MB-231 by Sulfasalazine and Ferric Ammonium Citrate
Date Issued
2016
Date
2016
Author(s)
Lin, Ya-Wei
Abstract
Iron plays dual roles in cells. It is essential for cell growth but also produce reactive oxygen species (ROS) via the Fenton reaction then inducing cell toxicity and damage. Iron-dependent cell death, ferroptosis, is a newly discovered non-apoptotic cell death mode in 2003. It is a regulated form of cell death driven by iron-induced lipid peroxide accumulation and regulation strictly by intracellular signaling pathway. The morphological, biochemical markers and genetic characteristics of ferroptosis are different from apoptosis, necrosis and autophagic. The mechanism of ferroptosis is inhibiting synthesis and utilization of reduced-glutathione (GSH) . Then, GSH depletion and lipid peroxide (LROS) accumulation lead to ferroptosis. Blockade of any steps is might prevent ferroptosis. Breast cancer cells have the ability of iron accumulation, which increases breast cancer cells growth. The higher malignancy degrees of breast cancer cells have the stronger ability of iron accumulation. Therefore, the purpose of this study is investigating the effect of ferroptosis on breast cancer cell. The study design is making use of the two characteristics of triple-negative breast cancer cell line MDA-MB-231 : sensitive to sulfasalazine (SAS) and strong ability of iron accumulation, to induce ferroptosis. We detect ferroptosis molecular characteristics, and the effects is blocked by specific inhibitors ferrostatin-1. Then, we analyze iron-related antioxidant proteins NRF2, HO-1 and ferritin (FTH) protein expression and assess the impact of the antioxidant mineral selenium and zinc compound in ferroptosis. The results show that combined group (SAS + iron) induce MDA-MB-231 cells ferroptosis, and ferrostatin-1 inhibit cell death. In addition, ROS and LROS are increased before cell death. The NRF2 and FTH protein expression levels are increased in a combined group dose-dependent manner. Finally, we found selenium can inhibit ferroptosis, and the mechanism may be through increasing the GPX4 protein expression. Zinc increase cell death in combined group and enhance Zn-MT protein expression, but Zn-MT does not contribute to prevent cell death.
Subjects
Ferroptosis
Iron
Breast Cancer
Sulfasalazine
SDGs
Type
thesis
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