Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10079)
Regulator Name Cathepsin B (CTSB)
Synonyms
CPSB; APP secretase; Cathepsin B1
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Gene Name CTSB
Gene ID 1508
Regulator Type Protein coding
Uniprot ID P07858
Sequence
MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCG
TFLGGPKPPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDR
ICIHTNAHVSVEVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYESHVGCR
PYSIPPCEHHVNGSRPPCTGEGDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIM
AEIYKNGPVEGAFSVYSDFLLYKSGVYQHVTGEMMGGHAIRILGWGVENGTPYWLVANSW
NTDWGDNGFFKILRGQDHCGIESEVVAGIPRTDQYWEKI

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Family Peptidase C1 family
Function
Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Cleaves matrix extracellular phosphoglycoprotein MEPE. Involved in the solubilization of cross-linked TG/thyroglobulin in the thyroid follicle lumen. Has also been implicated in tumor invasion and metastasis.

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HGNC ID
HGNC:2527
KEGG ID hsa:1508
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CTSB can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Drug Artesunate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
In Vivo Model
A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day.

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Response regulation Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Cathepsin B (CTSB) Protein coding
 Regulator Info 
Responsed Drug Artesunate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
In Vivo Model
A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day.

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Response regulation Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment.
Artesunate [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
In Vivo Model
A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day.

    Click to Show/Hide
Response regulation Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment.
References
Ref 1 Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma. Acta Pharmacol Sin. 2021 Feb;42(2):301-310. doi: 10.1038/s41401-020-0478-3. Epub 2020 Jul 22.