Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles.
Nanomedicine
; 55: 102714, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38738528
ABSTRACT
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 Fe3+ to Fe2+. Taken together, our data show that FeHA is capable of triggering cancer cell death in a KRAS-selective, STEAP3-dependent manner in PDAC cells.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Carcinoma Ductal Pancreático
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Ferroptose
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Ferro
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article