Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles.
Ferroptosis
KRAS
Nanomedicine
Pancreatic adenocarcinoma
STEAP3
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
28
05
2023
revised:
23
09
2023
accepted:
21
10
2023
medline:
13
5
2024
pubmed:
13
5
2024
entrez:
13
5
2024
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in KRAS mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type versus mutant KRAS. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe
Identifiants
pubmed: 38738528
pii: S1549-9634(23)00065-5
doi: 10.1016/j.nano.2023.102714
pii:
doi:
Substances chimiques
Iron
E1UOL152H7
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102714Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in the present paper.