The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells
Open accessAbstract
Ferroptosis is an iron-dependent, oxidative cell death, and is distinct from apoptosis, necrosis and autophagy. In this study, we demonstrated that lysosome disrupting agent, siramesine and a tyrosine kinase inhibitor, lapatinib synergistically induced cell death and reactive oxygen species (ROS) in MDA MB 231, MCF-7, ZR-75 and SKBr3 breast cancer cells over a 24 h time course. Furthermore, the iron chelator deferoxamine (DFO) significantly reduced cytosolic ROS and cell death following treatment with siramesine and lapatinib. Furthermore, we determined that FeCl3 levels were elevated in cells treated with siramesine and lapatinib indicating an iron-dependent cell death, ferroptosis. To confirm this, we treated cells with a potent inhibitor of ferroptosis, ferrastatin-1 that effectively inhibited cell death following siramesine and lapatinib treatment. The increase levels of iron could be due to changes in iron transport. We found that the expression of transferrin, which is responsible for the transport of iron into cells, is increased following treatment with lapatinib alone or in combination with siramesine. Knocking down of transferrin resulted in decreased cell death and ROS after treatment. In addition, ferroportin-1 (FPN) is an iron transport protein, responsible for removal of iron from cells. We found its expression is decreased after treatment with siramesine alone or in combination with lapatinib. Overexpression FPN resulted in decreased ROS and cell death whereas knockdown of FPN increased cell death after siramesine and lapatinib treatment. This indicates a novel induction of ferroptosis through altered iron regulation by treating breast cancer cells with a lysosome disruptor and a tyrosine kinase inhibitor.
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Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
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Regulation of Ferroptotic Cancer Cell Death by GPX4
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Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
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Ferroptosis as a p53-mediated activity during tumour suppression
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The role of iron and reactive oxygen species in cell death
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Glutaminolysis and transferrin regulate ferroptosis
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Cited by
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy
Gao, W., Wang, X., Zhou, Y., Wang, X., & Yu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01046-3 · Cited by 1,042
Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies
Zhou, Q., Meng, Y., Li, D., Yao, L., Le, J., Liu, Y., Sun, Y., Zeng, F., Chen, X., & Deng, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01769-5 · Cited by 890
Metadata
- Authors
- Ma, S., Henson, E. S., Chen, Y., & Gibson, S. B.
- Venue
- Cell Death & Disease
- Published
- 2016-07-21
- Volume
- 7
- Issue
- 7
- Pages
- e2307-e2307
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W2488521558
- Cited by
- 622
- References
- 50
- FWCI
- 12.71
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ma, S., Henson, E. S., Chen, Y., & Gibson, S. B. (2016). Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death & Disease. https://doi.org/10.1038/cddis.2016.208
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