ReferenceID 6030
Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth
Br J Cancer
Background: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. Methods: The ant
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- Reference Id
- 6030
- Evidence Id
- 22620
- Core Evidence Id
- 22620
- Source Reference Id
- 5324
- Herb2 Reference Id
- HBREF006121
- Subject Paper Key
- HBIN040266_35396498
- Pubmed Id
- 35396498
- Doi
- 10.1038/s41416-022-01800-y
- Paper Title
- Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth
- Paper Abstract
- Background: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. Methods: The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin. Results: Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death. Conclusions: Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate.
- Journal
- Br J Cancer
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Anti-glioma; Ferroptosis; Cancer; Glioma
- Paper Title Cn
- Paper Title En
- Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth
- Bilingual Status
- semi_complete