Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10494)
Regulator Name Carbonyl reductase [NADPH] 1 (CBR1)
Synonyms
15-hydroxyprostaglandin dehydrogenase [NADP(+)]; 20-beta-hydroxysteroid dehydrogenase; Alcohol dehydrogenase [NAD(P)+] CBR1; NADPH-dependent carbonyl reductase 1; Prostaglandin 9-ketoreductase; Prostaglandin-E(2) 9-reductase; Short chain dehydrogenase/reductase family 21C member 1
    Click to Show/Hide
Gene Name CBR1
Gene ID 873
Regulator Type Protein coding
Uniprot ID P16152
Sequence
MSSGIHVALVTGGNKGIGLAIVRDLCRLFSGDVVLTARDVTRGQAAVQQLQAEGLSPRFH
QLDIDDLQSIRALRDFLRKEYGGLDVLVNNAGIAFKVADPTPFHIQAEVTMKTNFFGTRD
VCTELLPLIKPQGRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMNKFVEDTK
KGVHQKEGWPSSAYGVTKIGVTVLSRIHARKLSEQRKGDKILLNACCPGWVRTDMAGPKA
TKSPEEGAETPVYLALLPPDAEGPHGQFVSEKRVEQW

    Click to Show/Hide
Family Short-chain dehydrogenases/reductases (SDR) family
Function
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione- conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione. In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue.

    Click to Show/Hide
HGNC ID
HGNC:1548
KEGG ID hsa:873
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CBR1 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).
Browse Target
Browse Disease
Browse Drug
Ferritin heavy chain (FTH1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Drug Chrysin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell proliferation
Cell autophagy
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Capan-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0026
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
AsPC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0152
In Vivo Model
Male BALB/c nude mice (5 weeks old, weighing 18-20 g) were provided by Jiangsu Jicui Yaokang Biotechnology Co., Ltd. (Nanjing, China). The mice were subcutaneously transplanted with non-targeting shRNA (shcontrol) or CBR1-targeting shRNA (shCBR1)-transfected PANC-1 cells (200 uL, 1 x 107 cells). Tumor volumes and body weights were measured every 4 days (n = 4, each), tumor volume = 0.5 x (a x a x b) (a, smallest diameter; b, largest diameter). The mice were subcutaneously inoculated with PANC-1 cells (200 uL, 1 x 107 cells) in the combination treatment. When the tumor volume reached 80-100 mm3, the mice were treated with chrysin (30 mg/kg/i.P., daily), gemcitabine (20 mg/kg/i.p., once every other day), or in combination for four weeks.

    Click to Show/Hide
Response regulation Inhibition of CBR1 by chrysin increased cellular ROS levels and led to ROS-dependent autophagy, which resulted in the degradation of ferritin heavy polypeptide 1 (FTH1) and an increase in the intracellular free iron level that participates in ferroptosis in pancreatic cancer (PC) cells. Finally, chrysin enhanced PC sensitivity to gemcitabine by inducing ferroptotic death in vitro and in vivo.?
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Carbonyl reductase [NADPH] 1 (CBR1) Protein coding
 Regulator Info 
Responsed Drug Chrysin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell proliferation
Cell autophagy
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Capan-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0026
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
AsPC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0152
In Vivo Model
Male BALB/c nude mice (5 weeks old, weighing 18-20 g) were provided by Jiangsu Jicui Yaokang Biotechnology Co., Ltd. (Nanjing, China). The mice were subcutaneously transplanted with non-targeting shRNA (shcontrol) or CBR1-targeting shRNA (shCBR1)-transfected PANC-1 cells (200 uL, 1 x 107 cells). Tumor volumes and body weights were measured every 4 days (n = 4, each), tumor volume = 0.5 x (a x a x b) (a, smallest diameter; b, largest diameter). The mice were subcutaneously inoculated with PANC-1 cells (200 uL, 1 x 107 cells) in the combination treatment. When the tumor volume reached 80-100 mm3, the mice were treated with chrysin (30 mg/kg/i.P., daily), gemcitabine (20 mg/kg/i.p., once every other day), or in combination for four weeks.

    Click to Show/Hide
Response regulation Inhibition of CBR1 by chrysin increased cellular ROS levels and led to ROS-dependent autophagy, which resulted in the degradation of ferritin heavy polypeptide 1 (FTH1) and an increase in the intracellular free iron level that participates in ferroptosis in pancreatic cancer (PC) cells. Finally, chrysin enhanced PC sensitivity to gemcitabine by inducing ferroptotic death in vitro and in vivo.?
Chrysin [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 Ferritin heavy chain (FTH1) Suppressor; Marker
 Target Info 
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell proliferation
Cell autophagy
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Capan-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0026
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
AsPC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0152
In Vivo Model
Male BALB/c nude mice (5 weeks old, weighing 18-20 g) were provided by Jiangsu Jicui Yaokang Biotechnology Co., Ltd. (Nanjing, China). The mice were subcutaneously transplanted with non-targeting shRNA (shcontrol) or CBR1-targeting shRNA (shCBR1)-transfected PANC-1 cells (200 uL, 1 x 107 cells). Tumor volumes and body weights were measured every 4 days (n = 4, each), tumor volume = 0.5 x (a x a x b) (a, smallest diameter; b, largest diameter). The mice were subcutaneously inoculated with PANC-1 cells (200 uL, 1 x 107 cells) in the combination treatment. When the tumor volume reached 80-100 mm3, the mice were treated with chrysin (30 mg/kg/i.P., daily), gemcitabine (20 mg/kg/i.p., once every other day), or in combination for four weeks.

    Click to Show/Hide
Response regulation Inhibition of CBR1 by chrysin increased cellular ROS levels and led to ROS-dependent autophagy, which resulted in the degradation of ferritin heavy polypeptide 1 (FTH1) and an increase in the intracellular free iron level that participates in ferroptosis in pancreatic cancer (PC) cells. Finally, chrysin enhanced PC sensitivity to gemcitabine by inducing ferroptotic death in vitro and in vivo.?
References
Ref 1 Chrysin induces autophagy-dependent ferroptosis to increase chemosensitivity to gemcitabine by targeting CBR1 in pancreatic cancer cells. Biochem Pharmacol. 2021 Nov;193:114813. doi: 10.1016/j.bcp.2021.114813. Epub 2021 Oct 18.