Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0436)
Name
zero-valent-iron nanoparticle
Drug Type
Small molecule
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
mTOR signaling pathway hsa04150
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
A9 cells Lung carcinoma Mus musculus CVCL_S007
MRC-5 cells Normal Homo sapiens CVCL_0440
IMR-90 cells Normal Homo sapiens CVCL_0347
In Vivo Model
5-6-week-old BALB/c nude mice (ZVI@Ag treatment) or NOD/SCID mice (ZVI@CMC treatment) were subcutaneously implanted with 1 x 106 H460 cells. For A549 xenograft model of immunodeficient mouse and spontaneous lung metastasis model, 5-6-week-old NOD/SCID mice were subcutaneously implanted with 5 x 106 A549 cells. For experimental lung metastasis model, H460 cells (1 x 106 cells/200 uL) were resuspended in serum-free medium and injected intravenously (i.v.) into tail-vein of NOD/SCID mice. For subcutaneous model of immunocompetent mouse, LLC cells (5 x 105) were injected into both flank of 6-week-old C57BL/6 mice.

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Response regulation Zero-valent-iron nanoparticle (ZVI-NP) triggered ferroptosis selectively in lung cancer cells by suppressing NRF2-mediated cytoprotection program, which was attributed to the ZVI-NP-induced disruption of PRKAA1 (AMPK)/mTOR signaling and activation of GSK3/-TrCP-dependent degradation system.
References
Ref 1 An innovative NRF2 nano-modulator induces lung cancer ferroptosis and elicits an immunostimulatory tumor microenvironment. Theranostics. 2021 May 13;11(14):7072-7091. doi: 10.7150/thno.57803. eCollection 2021.