Siramesine and lapatinib induce synergic cell death via a ferroptotic mechanism in lung adenocarcinoma and glioblastoma cells
Date
2017
Authors
Blankstein, Anna R.
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Abstract
In cancer cells, the most common forms of cell death are often actively inhibited, contributing to the development of drug resistance. Identifying and exploiting alternative cell death pathways are essential to overcoming or bypassing drug resistance. Ferroptosis, a newly described, morphologically and biochemically distinct, cell death mechanism is characterized by iron-dependent cellular accumulation of reactive oxygen species. The combination of siramesine, a lysosome disruptor, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced death in breast cancer cells. This cell death had characteristics of ferroptosis: it was blocked by the ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine. The objective of the present study was to determine whether lysosome disruptors and TKIs, in combination, would induce synergic cell death via a ferroptotic mechanism in lung adenocarcinoma and glioblastoma cells. Inducing ferroptosis could be a potential therapeutic strategy for these cancers that have limited available treatment options.
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Keywords
Cell death, Ferroptosis, Glioblastoma, Lung adenocarcinoma, Drug synergy, Drug repurposing