Erastin triggers autophagic death of breast cancer cells by increasing intracellular iron levels

Li,Mengxin; Wang,Xuanzhong; Lu,Shan; He,Chuan; Wang,Chongcheng; Wang,Lei; Wang,Xinyu; Ge,Pengfei; Song,Dong

doi:10.3892/ol.2020.11918

Erastin triggers autophagic death of breast cancer cells by increasing intracellular iron levels

Authors:
- Mengxin Li
- Xuanzhong Wang
- Shan Lu
- Chuan He
- Chongcheng Wang
- Lei Wang
- Xinyu Wang
- Pengfei Ge
- Dong Song
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Affiliations: Department of Breast Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Research Center of Neuroscience, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, Jilin 130022, P.R. China
Published online on: July 29, 2020 https://doi.org/10.3892/ol.2020.11918
Article Number: 57
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Erastin is a small molecular compound that induces ferroptosis by binding to voltage‑dependent anion‑selective channel protein (VDAC)2, VDAC3 and solute carrier family 7 member 5 inhibiting the cystine/glutamate antiporter. However, to the best of our knowledge, the mechanism of erastin‑induced breast cancer cell death remains unclear. In present study aimed to explore the underlying mechanisms of the antitumor effects of erastin on breast cancer cells. Cellular viability was assessed using an MTT assay, a lactate dehydrogenase cytotoxicity assay kit was used to determine the cell death rate, the intracellular Fe²⁺ levels were determined using an iron colorimetric assay kit and western blotting was used to estimate the changes of autophagy‑associated proteins levels. The present study demonstrated that erastin inhibited the viability of breast cancer cells and induced breast cancer cell death in a dose‑dependent manner. Additionally, autophagy was activated by erastin, as demonstrated by upregulated expression levels of autophagy‑associated proteins in breast cancer cells. Bafilomycin A1, 3‑methyladenine and knockdown of autophagy related (ATG)5 with small interfering RNA prevented erastin‑induced breast cancer cell death and inhibited the erastin‑induced changes in the expression levels of the autophagy‑associated proteins beclin1, ATG5, ATG12, microtubule‑associated proteins 1A/1B light chain 3B (LC3B) and P62. Furthermore, erastin‑induced breast cancer cell death was inhibited by an iron chelator, deferoxamine, which inhibited the increases of erastin‑induced iron levels and inhibited the erastin‑induced changes in the expression levels of the autophagy‑related proteins beclin1, ATG5, ATG12, LC3B and P62. In summary, erastin triggered autophagic death in breast cancer cells by increasing intracellular iron levels.

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