General Information of the Disease (ID: DIS00036)
Name
Squamous cell carcinoma of skin
ICD
ICD-11: 2C31
Full List of Target(s) of This Ferroptosis-centered Disease
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Driver
Responsed Disease Cutaneous squamous cell carcinoma [ICD-11: 2C31]
Responsed Drug Itraconazole Investigative
Responsed Regulator Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model A-431 cells Skin squamous cell carcinoma Homo sapiens CVCL_0037
COLO 16 cells Skin squamous cell carcinoma Homo sapiens CVCL_D607
In Vivo Model
Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily).

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Response regulation Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells.
References
Ref 1 Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis. Front Pharmacol. 2022 Feb 15;13:828983. doi: 10.3389/fphar.2022.828983. eCollection 2022.