Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10063)
Target Name Stearoyl-CoA desaturase (SCD)
Synonyms
FADS5; SCD1; SCDOS; hSCD1; Acyl-CoA desaturase; Delta(9)-desaturase (Delta-9 desaturase); Fatty acid desaturase
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Gene Name SCD
Sequence
MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYK
DKEGPSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAH
RLWSHRSYKARLPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFS
HVGWLLVRKHPAVKEKGSTLDLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGE
TFQNSVFVATFLRYAVVLNATWLVNSAAHLFGYRPYDKNISPRENILVSLGAVGEGFHNY
HHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRKKVSKAAILARIKRTGDGNYKSG

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Family Fatty acid desaturase type 1 family
Function
Stearoyl-CoA desaturase that utilizes O2 and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation. Plays an important role in body energy homeostasis. Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides.

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Gene ID 6319
Uniprot ID
O00767
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
SCD can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
Sterol regulatory element-binding protein 1 (SREBF1)
 Regulator Info 
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Drug Lactate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response Description The monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of SREBP1 (SREBF1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids.
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Drug NL01 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

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Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
Nonalcoholic fatty liver disease [ICD-11: DB92]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Regulator for Ferroptosis Suppressor
Responsed Drug D-(-)-Fructose Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model
 hLCs (Liver cells)
In Vivo Model
Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

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Response Description The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD).
Fibrosarcoma [ICD-11: 2B53]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [5]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
BT-474 cells Invasive breast carcinoma Homo sapiens CVCL_0179
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
U-87MG cells Glioblastoma Homo sapiens CVCL_GP63
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
DU145 cells Prostate carcinoma Homo sapiens CVCL_0105
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
LN-229 cells Glioblastoma Homo sapiens CVCL_0393
SK-MEL-2 cells (MEK inhibitor-resistant) cells Melanoma Homo sapiens CVCL_0069
In Vivo Model
For the in vivo xenograft mouse model, 17-b-estradiol 60-d release pellets (Innovative Research of America) were implanted subcutaneously into the left flank 7 d before tumor inoculation. GPX4 iKO BT474 cells were inoculated by injecting 5 x 106 cells in 50% Matrigel subcutaneously in the right flank of 6- to 8-wk-old female athymicnu/numice (Envigo). For PC-3 tumor models, male athymic nu/nu mice aged 5 to 6 wk were injected in the right flank with 5 x 106 PC-3 cells.

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Response Description Hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 inhibition with ferroptosis induction shows therapeutic promise of preclinical models in Fibrosarcoma.
Serine/threonine-protein kinase mTOR (MTOR)
 Regulator Info 
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [4]
Regulator for Ferroptosis Suppressor
Responsed Drug Everolimus Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 BON-1 cells Pancreatic serotonin-producing neuroendocrine tumor Homo sapiens CVCL_3985
QGP-1 cells Pancreatic somatostatinoma Homo sapiens CVCL_3143
Response Description The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pancreatic neuroendocrine tumors (pNETs) that targets mTOR signaling.
mmu-miR-33-5p (miRNA)
 Regulator Info 
Nonalcoholic fatty liver disease [ICD-11: DB92]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Regulator for Ferroptosis Driver
Responsed Drug D-(-)-Fructose Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model
 hLCs (Liver cells)
In Vivo Model
Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

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Response Description The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD).
Hydroxycarboxylic acid receptor 1 (HCAR1)
 Regulator Info 
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Drug Lactate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response Description Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Drug NL01 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

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Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
Regulatory-associated protein of mTOR (RPTOR)
 Regulator Info 
Fibrosarcoma [ICD-11: 2B53]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [5]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
BT-474 cells Invasive breast carcinoma Homo sapiens CVCL_0179
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
U-87MG cells Glioblastoma Homo sapiens CVCL_GP63
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
DU145 cells Prostate carcinoma Homo sapiens CVCL_0105
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
LN-229 cells Glioblastoma Homo sapiens CVCL_0393
SK-MEL-2 cells (MEK inhibitor-resistant) cells Melanoma Homo sapiens CVCL_0069
In Vivo Model
Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection).

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Response Description Hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 (RPTOR is a core component of mTORC1) inhibition with ferroptosis induction shows therapeutic promise of preclinical models in Fibrosarcoma.
Nuclear receptor subfamily 4 group A member 1 (NR4A1)
 Regulator Info 
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [6]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
SW1990 cells Pancreatic adenocarcinoma Homo sapiens CVCL_1723
Response Description FBW7 (FBXW7) inhibited the expression of stearoyl-CoA desaturase (SCD1) via inhibiting nuclear receptor subfamily 4 group A member 1 (NR4A1). SCD1 was reported to inhibit both ferroptosis and apoptosis. And activating ferroptosis and apoptosis immensely increased gemcitabine sensitivity, which might provide strategies for the combination therapy for pancreatic cancer.
Menin (MEN1)
 Regulator Info 
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [4]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 BON-1 cells Pancreatic serotonin-producing neuroendocrine tumor Homo sapiens CVCL_3985
QGP-1 cells Pancreatic somatostatinoma Homo sapiens CVCL_3143
Response Description We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling.
Membrane-spanning 4-domains subfamily A member 15 (MS4A15)
 Regulator Info 
Fibrosarcoma [ICD-11: 2B53]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [7]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell migration
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
HEK-293T cells Normal Homo sapiens CVCL_0063
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response Description MS4A15 regulation of anti-ferroptotic lipid reservoirs provides a key resistance mechanism that is distinct from antioxidant and lipid detoxification pathways. And Scd1 and Fads2 are counterregulated with Ms4a15 OE in Fibrosarcoma.
Lymphoid-specific helicase (HELLS)
 Regulator Info 
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [8]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 MRC-5 cells Normal Homo sapiens CVCL_0440
HBE1 cells Normal Homo sapiens CVCL_0287
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H522 cells Non-small cell lung carcinoma Homo sapiens CVCL_1567
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
95C cells Lung giant cell carcinoma Homo sapiens CVCL_7109
95D cells Lung giant cell carcinoma Homo sapiens CVCL_7110
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
SCID Mice (Hunan SJA Laboratory Animal Co.Ltd.) were injected with A549 (1 x 106 cells/mouse) or H358 (2 x 106 cells/mouse) cells via mammary fat pad (10 mice/group). Mice with A549 or H358 cells were imaged from dorsal and ventral views every three days.

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Response Description LSH (HELLS) is involved in ferroptosis and is a potential therapeutic target in cancer because of its crucial role in ferroptosis. LSH functioned as an oncogene in lung cancer in vitro and in vivo. And LSH promotes the lipid metabolic genes, including SCD1 and FADS2.
LINC01606 (IncRNA)
 Regulator Info 
Colon cancer [ICD-11: 2B90]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [9]
Regulator for Ferroptosis Suppressor
Pathway Response Wnt signaling pathway hsa04310
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell stemness
In Vitro Model
 SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.

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Response Description LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606.
hsa-miR-423-5p (miRNA)
 Regulator Info 
Colon cancer [ICD-11: 2B90]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [9]
Regulator for Ferroptosis Driver
Pathway Response Wnt signaling pathway hsa04310
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell stemness
In Vitro Model
 SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.

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Response Description LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606.
F-box/WD repeat-containing protein 7 (FBXW7)
 Regulator Info 
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [6]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
SW1990 cells Pancreatic adenocarcinoma Homo sapiens CVCL_1723
Response Description FBW7 (FBXW7) inhibited the expression of stearoyl-CoA desaturase (SCD1) via inhibiting nuclear receptor subfamily 4 group A member 1 (NR4A1). SCD1 was reported to inhibit both ferroptosis and apoptosis. And activating ferroptosis and apoptosis immensely increased gemcitabine sensitivity, which might provide strategies for the combination therapy for pancreatic cancer.
Unspecific Regulator
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [10]
Responsed Drug Sorafenib Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed.

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Response Description Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced Hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis.
Melanoma [ICD-11: 2C30]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [11]
Responsed Drug Lorlatinib Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
WM35 cells Melanoma Homo sapiens CVCL_0580
SK-MEL-5 cells Cutaneous melanoma Homo sapiens CVCL_0527
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal experiments were approved by the Ethical Review of Experimental Animals at Central South University. To generate subcutaneous tumors, 2 x 106 control A375 cells or GPX4 KO cells were suspended in 100 ul PBS and injected subcutaneously into nude mice (Shanghai SLAC). Tumor-bearing mice were randomly allocated into groups and treated with vehicle (2% DMSO + 30% PEG300, per day by orally) or lorlatinib (10 mg/kg, per day by orally). Liproxstatin-1 (10 mg/kg) was administrated through intraperitoneal injection per day. Tumors were weighted and photographed on day 18 after treatment. Tumor size were recorded every three days and calculated as [(length x width x width)/2].

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Response Description Lorlatinib sensitized melanoma to ferroptosis through targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis and its downstream SCD expression.
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [12]
Responsed Drug MI463 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR-4 cells Ovarian adenocarcinoma Homo sapiens CVCL_1627
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Lu-99 cells Lung giant cell carcinoma Homo sapiens CVCL_3015
Lu-65 cells Lung giant cell carcinoma Homo sapiens CVCL_1392
PC-7 cells Lung adenocarcinoma Homo sapiens CVCL_A786
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
CFPAC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_1119
Response Description The MI463 induced decrease in cell viability may be at least partly associated with the inhibition of SCD1 activity. In addition, the potent induction of HO1 contributed to the synergistic effects of MI463 plus auranofin. Therefore, meninMLL inhibitors, such as MI463, in combination with auranofin represent an effective therapeutic approach for several types of cancer via the induction of ferroptosis in High grade ovarian serous adenocarcinoma.
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [13]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
LL/2 (LLC1) cells Lung cancer Mus musculus CVCL_4358
HUVECs (Human umbilical vein endothelial cells)
In Vivo Model
For treatment with RSL3 (20 mg/kg), drug was administered in mice bearing LLC tumors by i.p. injection every other day for 2 weeks. For cisplatin, BALB/c mice bearing 4T1 tumors (50-100 mm3) were administered by i.p. injection of vehicle (0.7% DMSO in PBS) or cisplatin (7 mg/kg/week) for 3 weeks.

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Response Description SCD1 and FABP4 were also found upregulated in recurrent human breast cancer samples and correlated with worse prognosis of cancer patients with different types of tumors. Mechanistically, SCD1 leads to fatty acid (FA) desaturation and FABP4 derived from TEM enhances lipid droplet (LD) in cancer cells, which cooperatively protect from oxidative stress-induced ferroptosis.
Sterol regulatory element-binding protein 1 (SREBF1)
 Regulator Info 
Lactate [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response Description The monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of SREBP1 (SREBF1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids.
NL01 [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Disease Ovarian cancer [ICD-11: 2C73]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

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Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
D-(-)-Fructose [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Regulator for Ferroptosis Suppressor
Responsed Disease Nonalcoholic fatty liver disease [ICD-11: DB92]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model hLCs (Liver cells)
In Vivo Model
Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

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Response Description The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD).
Serine/threonine-protein kinase mTOR (MTOR)
 Regulator Info 
Everolimus [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [4]
Regulator for Ferroptosis Suppressor
Responsed Disease Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model BON-1 cells Pancreatic serotonin-producing neuroendocrine tumor Homo sapiens CVCL_3985
QGP-1 cells Pancreatic somatostatinoma Homo sapiens CVCL_3143
Response Description The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pancreatic neuroendocrine tumors (pNETs) that targets mTOR signaling.
mmu-miR-33-5p (miRNA)
 Regulator Info 
D-(-)-Fructose [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Regulator for Ferroptosis Driver
Responsed Disease Nonalcoholic fatty liver disease [ICD-11: DB92]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model hLCs (Liver cells)
In Vivo Model
Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

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Response Description The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD).
Hydroxycarboxylic acid receptor 1 (HCAR1)
 Regulator Info 
Lactate [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response Description Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
NL01 [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Disease Ovarian cancer [ICD-11: 2C73]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

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Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
Unspecific Regulator
Sorafenib [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [10]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed.

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Response Description Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced Hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis.
Lorlatinib [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [11]
Responsed Disease Melanoma [ICD-11: 2C30]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
WM35 cells Melanoma Homo sapiens CVCL_0580
SK-MEL-5 cells Cutaneous melanoma Homo sapiens CVCL_0527
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal experiments were approved by the Ethical Review of Experimental Animals at Central South University. To generate subcutaneous tumors, 2 x 106 control A375 cells or GPX4 KO cells were suspended in 100 ul PBS and injected subcutaneously into nude mice (Shanghai SLAC). Tumor-bearing mice were randomly allocated into groups and treated with vehicle (2% DMSO + 30% PEG300, per day by orally) or lorlatinib (10 mg/kg, per day by orally). Liproxstatin-1 (10 mg/kg) was administrated through intraperitoneal injection per day. Tumors were weighted and photographed on day 18 after treatment. Tumor size were recorded every three days and calculated as [(length x width x width)/2].

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Response Description Lorlatinib sensitized melanoma to ferroptosis through targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis and its downstream SCD expression.
MI463 [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [12]
Responsed Disease Ovarian cancer [ICD-11: 2C73]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR-4 cells Ovarian adenocarcinoma Homo sapiens CVCL_1627
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Lu-99 cells Lung giant cell carcinoma Homo sapiens CVCL_3015
Lu-65 cells Lung giant cell carcinoma Homo sapiens CVCL_1392
PC-7 cells Lung adenocarcinoma Homo sapiens CVCL_A786
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
CFPAC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_1119
Response Description The MI463 induced decrease in cell viability may be at least partly associated with the inhibition of SCD1 activity. In addition, the potent induction of HO1 contributed to the synergistic effects of MI463 plus auranofin. Therefore, meninMLL inhibitors, such as MI463, in combination with auranofin represent an effective therapeutic approach for several types of cancer via the induction of ferroptosis in High grade ovarian serous adenocarcinoma.
References
Ref 1 HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications. Cell Rep. 2020 Dec 8;33(10):108487. doi: 10.1016/j.celrep.2020.108487.
Ref 2 Curcumin derivative NL01 induces ferroptosis in ovarian cancer cells via HCAR1/MCT1 signaling. Cell Signal. 2023 Sep;109:110791. doi: 10.1016/j.cellsig.2023.110791. Epub 2023 Jul 3.
Ref 3 The role of microRNA-33 as a key regulator in hepatic lipogenesis signaling and a potential serological biomarker for NAFLD with excessive dietary fructose consumption in C57BL/6N mice. Food Funct. 2021 Jan 21;12(2):656-667. doi: 10.1039/d0fo02286a. Epub 2021 Jan 6.
Ref 4 MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors. Acta Biochim Biophys Sin (Shanghai). 2022 Nov 25;54(11):1599-1609. doi: 10.3724/abbs.2022162.
Ref 5 Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31189-31197. doi: 10.1073/pnas.2017152117. Epub 2020 Nov 23.
Ref 6 FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells. Redox Biol. 2021 Jan;38:101807. doi: 10.1016/j.redox.2020.101807. Epub 2020 Nov 24.
Ref 7 MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling. Cell Death Differ. 2022 Mar;29(3):670-686. doi: 10.1038/s41418-021-00883-z. Epub 2021 Oct 18.
Ref 8 EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes. Theranostics. 2017 Jul 23;7(13):3293-3305. doi: 10.7150/thno.19988. eCollection 2017.
Ref 9 Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/-catenin-TFE3 feedback loop signalling. Clin Transl Med. 2022 Apr;12(4):e752. doi: 10.1002/ctm2.752.
Ref 10 Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma. Acta Pharmacol Sin. 2023 Mar;44(3):622-634. doi: 10.1038/s41401-022-00981-9. Epub 2022 Sep 15.
Ref 11 Inhibiting SCD expression by IGF1R during lorlatinib therapy sensitizes melanoma to ferroptosis. Redox Biol. 2023 May;61:102653. doi: 10.1016/j.redox.2023.102653. Epub 2023 Mar 1.
Ref 12 MeninMLL inhibitors induce ferroptosis and enhance the antiproliferative activity of auranofin in several types of cancer cells. Int J Oncol. 2020 Oct;57(4):1057-1071. doi: 10.3892/ijo.2020.5116. Epub 2020 Aug 28.
Ref 13 Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Redox Biol. 2021 Jul;43:102006. doi: 10.1016/j.redox.2021.102006. Epub 2021 May 14.