Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles

Thanpisit Lomphithak, Apiwit Sae-Fung, Simone Sprio, Anna Tampieri, Siriporn Jitkaew, Bengt Fadeel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number102714
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume55
DOIs
StatePublished - Jan 2024

Keywords

  • Ferroptosis
  • KRAS
  • Nanomedicine
  • Pancreatic adenocarcinoma
  • STEAP3

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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