General Information of the Disease (ID: DIS00108)
Name
Hepatoblastoma
ICD
ICD-11: DB91
Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Acute liver failure [ICD-11: DB91]
Responsed Drug Glycyrrhizin Phase 3
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.

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Response regulation The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Responsed Disease Hepatoblastoma [ICD-11: DB91]
Responsed Regulator BH3-interacting domain death agonist (BID) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
Response regulation Quercetin induced EB-mediated lysosome activation and increased ferritin degradation leading to ferroptosis and Bid-involved apoptosis in hepatoblastoma cells.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Acute liver failure [ICD-11: DB91]
Responsed Drug Glycyrrhizin Phase 3
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.

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Response regulation The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased.
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Acute liver failure [ICD-11: DB91]
Responsed Regulator Histone-lysine N-methyltransferase EZH2 (EZH2) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hLCs (Liver cells)
mPHs (Mouse primary hepatocytes)
In Vivo Model
Male C57BL/6 mice (n = 20, 6-8-week-old, b.w. 18-23 g) were purchased from SJA Laboratory Animal Co Ltd., Changsha, Hunan, China. Mice were given 600 mg/kg D-GalN (Sigma-Aldrich) and 30 ug/kg LPS (Sigma-Aldrich) by intraperitoneal injection. Mice in Sham group were received saline injection. For Fer-1 treatment, mice were received 10 mg/kg Fer-1 at 1 h prior to D-GalN and LPS injection. The wild-type (WT) or HBx-Tg mice were then subjected to D-GalN and LPS administration. For GSK126 treatment, wild-type (WT) or HBx-Tg mice were received GSK126 (150 mg/kg) prior to D-GalN and LPS administration.

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Response regulation HBx facilitates ferroptosis in acute liver failure (ALF) via EZH2/H3K27me3-mediated SLC7A11 suppression.
References
Ref 1 Mechanism of glycyrrhizin on ferroptosis during acute liver failure by inhibiting oxidative stress. Mol Med Rep. 2019 Nov;20(5):4081-4090. doi: 10.3892/mmr.2019.10660. Epub 2019 Sep 10.
Ref 2 HBx facilitates ferroptosis in acute liver failure via EZH2 mediated SLC7A11 suppression. J Biomed Sci. 2021 Oct 6;28(1):67. doi: 10.1186/s12929-021-00762-2.
Ref 3 Quercetin induces p53-independent cancer cell death through lysosome activation by the transcription factor EB and Reactive Oxygen Species-dependent ferroptosis. Br J Pharmacol. 2021 Mar;178(5):1133-1148. doi: 10.1111/bph.15350. Epub 2021 Feb 2.