The iron chelator deferriferrichrysin induces paraptosis via extracellular signal-related kinase activation in cancer cells.
anticancer
cell death
cytoplasmic vacuolization
endoplasmic reticulum
iron chelator
paraptosis
Journal
Genes to cells : devoted to molecular & cellular mechanisms
ISSN: 1365-2443
Titre abrégé: Genes Cells
Pays: England
ID NLM: 9607379
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
revised:
08
05
2023
received:
17
03
2023
accepted:
22
05
2023
medline:
7
9
2023
pubmed:
2
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
Cancer cells generally exhibit increased iron uptake, which contributes to their abnormal growth and metastatic ability. Iron chelators have thus recently attracted attention as potential anticancer agents. Here, we show that deferriferrichrysin (Dfcy), a natural product from Aspergillus oryzae acts as an iron chelator to induce paraptosis (a programmed cell death pathway characterized by ER dilation) in MCF-7 human breast cancer cells and H1299 human lung cancer cells. We first examined the anticancer efficacy of Dfcy in cancer cells and found that Dfcy induced ER dilation and reduced the number of viable cells. Extracellular signal-related kinase (ERK) was activated by Dfcy treatment, and the MEK inhibitor U0126, a small molecule commonly used to inhibit ERK activity, prevented the increase in ER dilation in Dfcy-treated cells. Concomitantly, the decrease in the number of viable cells upon treatment with Dfcy was attenuated by U0126. Taken together, these results demonstrate that the iron chelator Dfcy exhibits anticancer effects via induction of ERK-dependent paraptosis.
Substances chimiques
U 0126
0
deferriferrichrysin
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Iron Chelating Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
653-662Subventions
Organisme : Asahi Glass Foundation
Organisme : Hirao Taro Foundation of Konan Gakuen for Academic Research
Organisme : Japan Society for the Promotion of Science
ID : 18K06231
Organisme : Japan Society for the Promotion of Science
ID : 20K21259
Organisme : Japan Society for the Promotion of Science
ID : 21H02062
Organisme : Japan Society for the Promotion of Science
ID : 21K06158
Organisme : Japan Society for the Promotion of Science
ID : 22K08293
Organisme : JST SPRING
ID : JPMJSP2117
Informations de copyright
© 2023 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
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