Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10275)

Regulator Name	NAD-dependent protein deacylase sirtuin-6 (SIRT6)
Synonyms	NAD-dependent protein deacetylase sirtuin-6; SIR2-like protein 6 Click to Show/Hide
Gene Name	SIRT6
Gene ID	51548
Regulator Type	Protein coding
Uniprot ID	Q8N6T7
Sequence	MSVNYAAGLSPYADKGKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGISTASG IPDFRGPHGVWTMEERGLAPKFDTTFESARPTQTHMALVQLERVGLLRFLVSQNVDGLHV RSGFPRDKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTVAKARGLRACRGE LRDTILDWEDSLPDRDLALADEASRNADLSITLGTSLQIRPSGNLPLATKRRGGRLVIVN LQPTKHDRHADLRIHGYVDEVMTRLMKHLGLEIPAWDGPRVLERALPPLPRPPTPKLEPK EESPTRINGSIPAGPKQEPCAQHNGSEPASPKRERPTSPAPHRPPKRVKAKAVPS Click to Show/Hide
Family	Sirtuin family
Function	NAD-dependent protein deacetylase, deacylase and mono-ADP- ribosyltransferase that plays an essential role in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis and aging. Displays protein- lysine deacetylase or defatty-acylase (demyristoylase and depalmitoylase) activity, depending on the context. Acts as a key histone deacetylase by catalyzing deacetylation of histone H3 at 'Lys-9', 'Lys-18' and 'Lys- 56' (H3K9ac, H3K18ac and H3K56ac, respectively), suppressing target gene expression of several transcription factors, including NF-kappa-B. Acts as an inhibitor of transcription elongation by mediating deacetylation of H3K9ac and H3K56ac, preventing release of NELFE from chromatin and causing transcriptional pausing. Involved in DNA repair by promoting double-strand break (DSB) repair: acts as a DSB sensor by recognizing and binding DSB sites, leading to (1) recruitment of DNA repair proteins, such as SMARCA5/SNF2H, and (2) deacetylation of histone H3K9ac and H3K56ac. SIRT6 participation to DSB repair is probably involved in extension of life span. Also promotes DNA repair by deacetylating non-histone proteins, such as DDB2 and p53/TP53. Specifically deacetylates H3K18ac at pericentric heterochromatin, thereby maintaining pericentric heterochromatin silencing at centromeres and protecting against genomic instability and cellular senescence. Involved in telomere maintenance by catalyzing deacetylation of histone H3 in telomeric chromatin, regulating telomere position effect and telomere movement in response to DNA damage. Required for embryonic stem cell differentiation by mediating histone deacetylation of H3K9ac. Plays a major role in metabolism by regulating processes such as glycolysis, gluconeogenesis, insulin secretion and lipid metabolism. Inhibits glycolysis via histone deacetylase activity and by acting as a corepressor of the transcription factor HIF1A, thereby controlling the expression of multiple glycolytic genes. Has tumor suppressor activity by repressing glycolysis, thereby inhibiting the Warburg effect. Also regulates glycolysis and tumorigenesis by mediating deacetylation and nuclear export of non- histone proteins, such as isoform M2 of PKM (PKM2). Acts as a negative regulator of gluconeogenesis by mediating deacetylation of non-histone proteins, such as FOXO1 and KAT2A/GCN5. Promotes beta-oxidation of fatty acids during fasting by catalyzing deacetylation of NCOA2, inducing coactivation of PPARA. Acts as a regulator of lipid catabolism in brown adipocytes, both by catalyzing deacetylation of histones and non-histone proteins, such as FOXO1. Also acts as a regulator of circadian rhythms, both by regulating expression of clock-controlled genes involved in lipid and carbohydrate metabolism, and by catalyzing deacetylation of PER2. The defatty-acylase activity is specifically involved in regulation of protein secretion. Has high activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as RRAS2 and TNF, thereby regulating their secretion. Also acts as a mono-ADP- ribosyltransferase by mediating mono-ADP-ribosylation of PARP1, TRIM28/KAP1 or SMARCC2/BAF170. Mono-ADP-ribosyltransferase activity is involved in DNA repair, cellular senescence, repression of LINE-1 retrotransposon elements and regulation of transcription. Click to Show/Hide
HGNC ID	HGNC:14934
KEGG ID	hsa:51548

Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)

SIRT6 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

Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]

Target Info

In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Cataract		ICD-11: 9B10	Disease Info
Responsed Drug	Melatonin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[3]
Target for Ferroptosis	Suppressor
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Pathways in cancer			hsa05200
Cell Process	Cell ferroptosis
In Vitro Model	NCI-N87 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
Response regulation	SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in gastric cancer.

Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[2]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Responsed Drug	Isoorientin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	The A549/DDP tumor cells were subcutaneously injected (2 x 10⁶ cells/mL) into BALB/c-nu mice under aseptic conditions. 6 days later, the average diameter of the tumor reaches 0.5 cm, and the mice were randomly divided into the 1 mg/kg DDP group and the 1 mg/kg DDP + 25mg/kg IO group. Six mice from each group were intraperitoneally administered medications every 2 days for a total of 10 doses each. Click to Show/Hide
Response regulation	Isoorientin (IO) can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application.

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	Cataract		ICD-11: 9B10	Disease Info
Responsed Drug	Melatonin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.

Nuclear receptor coactivator 4 (NCOA4) [Driver]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[4]
Target for Ferroptosis	Driver
Responsed Disease	Thyroid cancer		ICD-11: 2D10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	CAL62 cells	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_1112
	BHT101 cells	Anaplastic thyroid carcinoma	Homo sapiens	CVCL_1085
In Vivo Model	Six-week-old male BALB/c-nu mice were provided by Beijing Vital River Laboratory Animal Technology Co. Ltd. All mice were randomly divided into 6 equal groups (CAL62-NC-Blank, CAL62-NC-sulfasalazine, CAL62-NC-sulfasalazine + CQ; CAL62-SIRT6-Blank, CAL62-SIRT6-sulfasalazine, CAL62-SIRT6-sulfasalazine + CQ). CAL62-NC or CAL62-SIRT6 cells (5 x 10⁶) suspended in 100 ul PBS were injected subcutaneously into the axilla of each nude mouse. After 5 days, the mice were treated with different reagents: solvent (100 ul 0.1 M NaOH and 100 ul saline), sulfasalazine (200 mg/kg, i.p., dissolved in 100 ul 0.1 M NaOH), CQ (50 mg/kg, i.p., dissolved in 100 ul saline). Click to Show/Hide
Response regulation	SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells in vivo.

Unspecific Target [Unspecific Target]

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[5]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Ferroptosis			hsa04216
	NF-kappa B signaling pathway			hsa04064
	Gluconeogenesis			hsa00010
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	SW1990 cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	PC-2 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_S970
	HPDE cells	Normal	Homo sapiens	CVCL_4376
In Vivo Model	A total of 20 SPF BALB/C nude mice were randomly divided into two groups [SIRT6 group (n = 10) and vector group (n = 10)]. PANC-1 cells (1 x 10⁶) in 200 ul phosphate-buffered saline were subcutaneously inoculated in nude mice of each group. The tumor volume was recorded every 7 days. Click to Show/Hide
Response regulation	SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-B signaling pathway in pancreatic cancer (PC). These findings suggested that SIRT6 may become a therapeutic target for PC.

Lung cancer [ICD-11: 2C25]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Responsed Drug	Isoorientin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	The A549/DDP tumor cells were subcutaneously injected (2 x 10⁶ cells/mL) into BALB/c-nu mice under aseptic conditions. 6 days later, the average diameter of the tumor reaches 0.5 cm, and the mice were randomly divided into the 1 mg/kg DDP group and the 1 mg/kg DDP + 25mg/kg IO group. Six mice from each group were intraperitoneally administered medications every 2 days for a total of 10 doses each. Click to Show/Hide
Response regulation	Isoorientin (IO) can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application.

Cataract [ICD-11: 9B10]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Responsed Drug	Melatonin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Responsed Drug	Melatonin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.

Gastric cancer [ICD-11: 2B72]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[3]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Pathways in cancer			hsa05200
Cell Process	Cell ferroptosis
In Vitro Model	NCI-N87 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
Response regulation	SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in gastric cancer.

Thyroid cancer [ICD-11: 2D10]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[4]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	CAL62 cells	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_1112
	BHT101 cells	Anaplastic thyroid carcinoma	Homo sapiens	CVCL_1085
In Vivo Model	Six-week-old male BALB/c-nu mice were provided by Beijing Vital River Laboratory Animal Technology Co. Ltd. All mice were randomly divided into 6 equal groups (CAL62-NC-Blank, CAL62-NC-sulfasalazine, CAL62-NC-sulfasalazine + CQ; CAL62-SIRT6-Blank, CAL62-SIRT6-sulfasalazine, CAL62-SIRT6-sulfasalazine + CQ). CAL62-NC or CAL62-SIRT6 cells (5 x 10⁶) suspended in 100 ul PBS were injected subcutaneously into the axilla of each nude mouse. After 5 days, the mice were treated with different reagents: solvent (100 ul 0.1 M NaOH and 100 ul saline), sulfasalazine (200 mg/kg, i.p., dissolved in 100 ul 0.1 M NaOH), CQ (50 mg/kg, i.p., dissolved in 100 ul saline). Click to Show/Hide
Response regulation	SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells 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				[5]
Target Regulator	NAD-dependent protein deacylase sirtuin-6 (SIRT6)		Protein coding	Regulator Info
Pathway Response	Ferroptosis			hsa04216
	NF-kappa B signaling pathway			hsa04064
	Gluconeogenesis			hsa00010
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	SW1990 cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	PC-2 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_S970
	HPDE cells	Normal	Homo sapiens	CVCL_4376
In Vivo Model	A total of 20 SPF BALB/C nude mice were randomly divided into two groups [SIRT6 group (n = 10) and vector group (n = 10)]. PANC-1 cells (1 x 10⁶) in 200 ul phosphate-buffered saline were subcutaneously inoculated in nude mice of each group. The tumor volume was recorded every 7 days. Click to Show/Hide
Response regulation	SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-B signaling pathway in pancreatic cancer (PC). These findings suggested that SIRT6 may become a therapeutic target for PC.

Isoorientin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[2]
Drug for Ferroptosis	Inducer
Response Target	Nuclear factor erythroid 2-related factor 2 (NFE2L2)		Suppressor; Marker	Target Info
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	The A549/DDP tumor cells were subcutaneously injected (2 x 10⁶ cells/mL) into BALB/c-nu mice under aseptic conditions. 6 days later, the average diameter of the tumor reaches 0.5 cm, and the mice were randomly divided into the 1 mg/kg DDP group and the 1 mg/kg DDP + 25mg/kg IO group. Six mice from each group were intraperitoneally administered medications every 2 days for a total of 10 doses each. Click to Show/Hide
Response regulation	Isoorientin (IO) can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application.

Melatonin [Investigative]

Drug Info

In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[1]
Drug for Ferroptosis	Suppressor
Response Target	Phospholipid hydroperoxide glutathione peroxidase (GPX4)		Suppressor	Target Info
Responsed Disease	Cataract		ICD-11: 9B10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.
Experiment 2 Reporting the Ferroptosis-centered Drug Response				[1]
Drug for Ferroptosis	Suppressor
Response Target	Ferritin heavy chain (FTH1)		Suppressor; Marker	Target Info
Responsed Disease	Cataract		ICD-11: 9B10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	B-3 cells	Normal	Homo sapiens	CVCL_6367
In Vivo Model	Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. Click to Show/Hide
Response regulation	Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats.

References

Ref 1	Melatonin inhibits ferroptosis and delays age-related cataract by regulating SIRT6/p-Nrf2/GPX4 and SIRT6/NCOA4/FTH1 pathways. Biomed Pharmacother. 2023 Jan;157:114048. doi: 10.1016/j.biopha.2022.114048. Epub 2022 Dec 1.
Ref 2	Isoorientin reverses lung cancer drug resistance by promoting ferroptosis via the SIRT6/Nrf2/GPX4 signaling pathway. Eur J Pharmacol. 2023 Sep 5;954:175853. doi: 10.1016/j.ejphar.2023.175853. Epub 2023 Jun 16.
Ref 3	SIRT6 silencing overcomes resistance to sorafenib by promoting ferroptosis in gastric cancer. Biochem Biophys Res Commun. 2021 Nov 5;577:158-164. doi: 10.1016/j.bbrc.2021.08.080. Epub 2021 Aug 30.
Ref 4	SIRT6 drives sensitivity to ferroptosis in anaplastic thyroid cancer through NCOA4-dependent autophagy. Am J Cancer Res. 2023 Feb 15;13(2):464-474. eCollection 2023.
Ref 5	SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF-B pathway. Exp Ther Med. 2022 Jun 8;24(2):502. doi: 10.3892/etm.2022.11430. eCollection 2022 Aug.

Ferroptosis Regulator Information

About FERREG

Visitor Map

Correspondence

Prof. Shuiping Liu