Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential.
Animals
Antineoplastic Agents, Phytogenic
/ pharmacology
Cell Movement
/ drug effects
Female
Ferroptosis
/ drug effects
G2 Phase Cell Cycle Checkpoints
/ drug effects
Hep G2 Cells
Humans
Lipid Peroxidation
/ drug effects
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
Nasopharyngeal Carcinoma
/ drug therapy
Nasopharyngeal Neoplasms
/ drug therapy
Neoplasm Invasiveness
Phospholipid Hydroperoxide Glutathione Peroxidase
/ genetics
Triterpenes
/ pharmacology
Tumor Burden
/ drug effects
Xenograft Model Antitumor Assays
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
04 03 2021
04 03 2021
Historique:
received:
29
06
2020
accepted:
09
02
2021
revised:
04
02
2021
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
14
9
2021
Statut:
epublish
Résumé
Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products.
Identifiants
pubmed: 33664249
doi: 10.1038/s41419-021-03516-y
pii: 10.1038/s41419-021-03516-y
pmc: PMC7933245
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Triterpenes
0
cucurbitacin B
0115W5MABF
Phospholipid Hydroperoxide Glutathione Peroxidase
EC 1.11.1.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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