Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis Journal Article

   

Authors:	Chen, G. Q.; Benthani, F. A.; Wu, J.; Liang, D.; Bian, Z. X.; Jiang, X.
Article Title:	Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis
Abstract:	The antimalarial drug artemisinin and its derivatives have been explored as potential anticancer agents, but their underlying mechanisms are controversial. In this study, we found that artemisinin compounds can sensitize cancer cells to ferroptosis, a new form of programmed cell death driven by iron-dependent lipid peroxidation. Mechanistically, dihydroartemisinin (DAT) can induce lysosomal degradation of ferritin in an autophagy-independent manner, increasing the cellular free iron level and causing cells to become more sensitive to ferroptosis. Further, by associating with cellular free iron and thus stimulating the binding of iron-regulatory proteins (IRPs) with mRNA molecules containing iron-responsive element (IRE) sequences, DAT impinges on IRP/IRE-controlled iron homeostasis to further increase cellular free iron. Importantly, in both in vitro and a mouse xenograft model in which ferroptosis was triggered in cancer cells by the inducible knockout of GPX4, we found that DAT can augment GPX4 inhibition-induced ferroptosis in a cohort of cancer cells that are otherwise highly resistant to ferroptosis. Collectively, artemisinin compounds can sensitize cells to ferroptosis by regulating cellular iron homeostasis. Our findings can be exploited clinically to enhance the effect of future ferroptosis-inducing cancer therapies. © 2019, ADMC Associazione Differenziamento e Morte Cellulare.
Journal Title:	Cell Death and Differentiation
Volume:	27
Issue:	1
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Date Published:	2020-01-01
Start Page:	242
End Page:	254
Language:	English
DOI:	10.1038/s41418-019-0352-3
PUBMED:	31114026
PROVIDER:	scopus
PMCID:	PMC7205875
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066888302&doi=10.1038%2fs41418-019-0352-3&partnerID=40&md5=a08a74e648d31bb0b0936dfaf1ccb03c
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/157731