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Huaier-derived arnicolide D induces ferroptosis in gastric cancer via SRC/TNF-mediated GPX4 inactivation - PubMed

7 hours ago
  • #arnicolide-D
  • #gastric-cancer
  • #ferroptosis
  • Huaier-derived arnicolide D induces ferroptosis in gastric cancer via SRC/TNF-mediated GPX4 inactivation.
  • Huaier n-butanol extract (HBE) shows anticancer activity but its bioactive components and mechanisms are not fully understood.
  • The study aimed to identify HBE's bioactive components and their ferroptosis-related mechanisms in gastric cancer treatment.
  • Methods included in vivo mouse models, UHPLC-MS/MS, network pharmacology, cellular assays, molecular docking, and gene knockdown.
  • HBE inhibited tumor growth by inducing ferroptosis, evidenced by increased 4-HNE levels and disrupted iron metabolism.
  • Arnicolide D was identified as a key active component in HBE with potent antitumor activity in vitro and in vivo.
  • Arnicolide D targets TNF and SRC, suppressing GPX4 expression at transcriptional and post-translational levels to promote ferroptosis.
  • The findings highlight Arnicolide D as a promising dual-target ferroptosis inducer for gastric cancer treatment.