Language:

Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis

Cell death and differentiation, 2020-01, Vol.27 (1), p.242-254 [Peer Reviewed Journal]

ADMC Associazione Differenziamento e Morte Cellulare 2019. ;ADMC Associazione Differenziamento e Morte Cellulare 2019 ;ISSN: 1350-9047 ;EISSN: 1476-5403 ;DOI: 10.1038/s41418-019-0352-3 ;PMID: 31114026

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis
Author: Chen, Guo-Qing ; Benthani, Fahad A ; Wu, Jiao ; Liang, Deguang ; Bian, Zhao-Xiang ; Jiang, Xuejun
Subjects: Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Artemisinin ; Artemisinins - chemistry ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Autophagy - drug effects ; Cancer ; Cell Line, Tumor ; Female ; Ferroptosis - drug effects ; Homeostasis ; Humans ; Iron - metabolism ; Iron-Regulatory Proteins - metabolism ; Lysosomes - metabolism ; Mice, Nude ; Neoplasms - metabolism ; Response Elements
Is Part Of: Cell death and differentiation, 2020-01, Vol.27 (1), p.242-254
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 1350-9047
EISSN: 1476-5403
DOI: 10.1038/s41418-019-0352-3
PMID: 31114026
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
ProQuest Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis

ADMC Associazione Differenziamento e Morte Cellulare 2019. ;ADMC Associazione Differenziamento e Morte Cellulare 2019 ;ISSN: 1350-9047 ;EISSN: 1476-5403 ;DOI: 10.1038/s41418-019-0352-3 ;PMID: 31114026

Searching Remote Databases, Please Wait