Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10207)

Regulator Name	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)
Synonyms	AMPK1; Acetyl-CoA carboxylase kinase; Hydroxymethylglutaryl-CoA reductase kinase; Tau-protein kinase PRKAA1 Click to Show/Hide
Gene Name	PRKAA1
Gene ID	5562
Regulator Type	Protein coding
Uniprot ID	Q13131
Sequence	MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNR QKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNG RLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEF LRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDG IFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMID DEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDS FLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDI MAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDE ITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPG SHTIEFFEMCANLIKILAQ Click to Show/Hide
Family	CAMK Ser/Thr protein kinase family
Function	Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45/WIPI4. Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Click to Show/Hide
HGNC ID	HGNC:9376
KEGG ID	hsa:5562

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

PRKAA1 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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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Intracerebral hemorrhage		ICD-11: 8B00	Disease Info
Responsed Drug	Artesunate		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
In Vivo Model	Rats were anaesthetised through intraperitoneal injection of pentobarbital (40 mg/kg) and placed onto a stereotaxic instrument (RWD Life Science Co., Ltd.). A 1-cm midline incision was performed in the rat scalp to expose the intersection point. Then, a hole 3.2 mm lateral and 1.4 mm anterior to the right bregma was produced. Next, 1.0 ul collagenase type IV (0.25 IU/ul; C5138; Sigma-Aldrich, USA) was injected into the basal ganglia via a microinjection pump (4.2 mm depth below the endocranium) at a rate of 0.2 ul/min. The needle was maintained for 5 min after injection to prevent backflow. Thereafter, the skin incision was closed using sutures. Rats in the sham group received 1.0 ul saline instead of collagenase type IV. Click to Show/Hide
Response regulation	Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway

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

Target Info

In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[2]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Responsed Drug	Ascorbic Acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[3]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Responsed Drug	zero-valent-iron nanoparticle		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	mTOR signaling pathway			hsa04150
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A9 cells	Lung carcinoma	Mus musculus	CVCL_S007
	MRC-5 cells	Normal	Homo sapiens	CVCL_0440
	IMR-90 cells	Normal	Homo sapiens	CVCL_0347
In Vivo Model	5-6-week-old BALB/c nude mice (ZVI@Ag treatment) or NOD/SCID mice (ZVI@CMC treatment) were subcutaneously implanted with 1 x 10⁶ H460 cells. For A549 xenograft model of immunodeficient mouse and spontaneous lung metastasis model, 5-6-week-old NOD/SCID mice were subcutaneously implanted with 5 x 10⁶ A549 cells. For experimental lung metastasis model, H460 cells (1 x 10⁶ cells/200 uL) were resuspended in serum-free medium and injected intravenously (i.v.) into tail-vein of NOD/SCID mice. For subcutaneous model of immunocompetent mouse, LLC cells (5 x 10⁵) were injected into both flank of 6-week-old C57BL/6 mice. Click to Show/Hide
Response regulation	Zero-valent-iron nanoparticle (ZVI-NP) triggered ferroptosis selectively in lung cancer cells by suppressing NRF2-mediated cytoprotection program, which was attributed to the ZVI-NP-induced disruption of PRKAA1 (AMPK)/mTOR signaling and activation of GSK3/-TrCP-dependent degradation system.

Heme oxygenase 1 (HMOX1) [Driver; Suppressor]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[2]
Target for Ferroptosis	Driver
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Responsed Drug	Ascorbic Acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.

Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[4]
Target for Ferroptosis	Suppressor
Responsed Disease	Multiple myeloma		ICD-11: 2A83	Disease Info
Responsed Drug	Fingolimod		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
Response regulation	Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.

Unspecific Target [Unspecific Target]

In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[5]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Responsed Drug	Dihydroartemisinin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell proliferation
	Cell cycle
In Vitro Model	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	KG1 cells	Normal	Mus musculus	CVCL_UD72
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In Vivo Model	BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 10⁷, suspended in 0.1 mL PBS). After tumors reached 100-200 mm³, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper. Click to Show/Hide
Response regulation	Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[6]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Responsed Drug	Typhaneoside		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
	AMPK signaling pathway			hsa04152
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell autophagy
In Vitro Model	KAS-6/1 cells	Plasma cell myeloma	Homo sapiens	CVCL_9544
	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	NB4 cells	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	4-week-old BALB/c malenude mice(Peking University Health Science Center, Beijing, China) were subcutaneously injection with HL60 cells (1 x 10⁷). After tumor volume reached 50 mm³, mice were randomly divided into 4 groups (n = 16/group). TYP was administered intraperitoneal injection once a day at 10, 20 and 30 mg/kg body weight and the mice in normal control group were received equal amounts of 10% DMSO in sterile corn oil. Click to Show/Hide
Response regulation	Typhaneoside (TYP) significantly triggered autophagy in acute myeloid leukemia (AML) cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately.
Experiment 3 Reporting the Ferroptosis Target of This Regulator				[7]
Responsed Disease	Corpus uteri cancer		ICD-11: 2C76	Disease Info
Responsed Drug	Amentoflavone		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hESCs (Human endometrial stromal cells)
	KLE cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
Response regulation	Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.
Experiment 4 Reporting the Ferroptosis Target of This Regulator				[8]
Responsed Disease	Cardiomyopathy		ICD-11: BC43	Disease Info
Responsed Drug	Salidroside		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male C57/BL mice (aged between 6 and 8 weeks and weighing 20 ± 2 g) were randomly divided into 6 groups (n = 6 mice per group) with equal number of mice in each group. The groups included saline control group (control group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days; DOX model group (DOX group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days and a single intraperitoneal administration of 10 mgxkg-1 DOX (HY-15,142, MCE, China) to the mice on the seventh day. Click to Show/Hide
Response regulation	Salidroside markedly down-regulated ferroptotic cell death by activating AMPK-dependent signaling pathways including regulating abnormal fatty acid metabolism and maintaining mitochondrial function. Therefore, salidroside is can be exploited to develop a novel medication for clinical Doxorubicin-induced cardiotoxicity.

Multiple myeloma [ICD-11: 2A83]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[4]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Fingolimod		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
Response regulation	Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.

Pancreatic cancer [ICD-11: 2C10]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Ascorbic Acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Ascorbic Acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.

Lung cancer [ICD-11: 2C25]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[3]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	zero-valent-iron nanoparticle		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	mTOR signaling pathway			hsa04150
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A9 cells	Lung carcinoma	Mus musculus	CVCL_S007
	MRC-5 cells	Normal	Homo sapiens	CVCL_0440
	IMR-90 cells	Normal	Homo sapiens	CVCL_0347
In Vivo Model	5-6-week-old BALB/c nude mice (ZVI@Ag treatment) or NOD/SCID mice (ZVI@CMC treatment) were subcutaneously implanted with 1 x 10⁶ H460 cells. For A549 xenograft model of immunodeficient mouse and spontaneous lung metastasis model, 5-6-week-old NOD/SCID mice were subcutaneously implanted with 5 x 10⁶ A549 cells. For experimental lung metastasis model, H460 cells (1 x 10⁶ cells/200 uL) were resuspended in serum-free medium and injected intravenously (i.v.) into tail-vein of NOD/SCID mice. For subcutaneous model of immunocompetent mouse, LLC cells (5 x 10⁵) were injected into both flank of 6-week-old C57BL/6 mice. Click to Show/Hide
Response regulation	Zero-valent-iron nanoparticle (ZVI-NP) triggered ferroptosis selectively in lung cancer cells by suppressing NRF2-mediated cytoprotection program, which was attributed to the ZVI-NP-induced disruption of PRKAA1 (AMPK)/mTOR signaling and activation of GSK3/-TrCP-dependent degradation system.

Intracerebral hemorrhage [ICD-11: 8B00]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Artesunate		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
In Vivo Model	Rats were anaesthetised through intraperitoneal injection of pentobarbital (40 mg/kg) and placed onto a stereotaxic instrument (RWD Life Science Co., Ltd.). A 1-cm midline incision was performed in the rat scalp to expose the intersection point. Then, a hole 3.2 mm lateral and 1.4 mm anterior to the right bregma was produced. Next, 1.0 ul collagenase type IV (0.25 IU/ul; C5138; Sigma-Aldrich, USA) was injected into the basal ganglia via a microinjection pump (4.2 mm depth below the endocranium) at a rate of 0.2 ul/min. The needle was maintained for 5 min after injection to prevent backflow. Thereafter, the skin incision was closed using sutures. Rats in the sham group received 1.0 ul saline instead of collagenase type IV. Click to Show/Hide
Response regulation	Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway

Acute myeloid leukaemia [ICD-11: 2A60]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[5]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Dihydroartemisinin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell proliferation
	Cell cycle
In Vitro Model	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	KG1 cells	Normal	Mus musculus	CVCL_UD72
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In Vivo Model	BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 10⁷, suspended in 0.1 mL PBS). After tumors reached 100-200 mm³, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper. Click to Show/Hide
Response regulation	Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[6]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Typhaneoside		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
	AMPK signaling pathway			hsa04152
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell autophagy
In Vitro Model	KAS-6/1 cells	Plasma cell myeloma	Homo sapiens	CVCL_9544
	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	NB4 cells	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	4-week-old BALB/c malenude mice(Peking University Health Science Center, Beijing, China) were subcutaneously injection with HL60 cells (1 x 10⁷). After tumor volume reached 50 mm³, mice were randomly divided into 4 groups (n = 16/group). TYP was administered intraperitoneal injection once a day at 10, 20 and 30 mg/kg body weight and the mice in normal control group were received equal amounts of 10% DMSO in sterile corn oil. Click to Show/Hide
Response regulation	Typhaneoside (TYP) significantly triggered autophagy in acute myeloid leukemia (AML) cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately.

Corpus uteri cancer [ICD-11: 2C76]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[7]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Amentoflavone		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hESCs (Human endometrial stromal cells)
	KLE cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
Response regulation	Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.

Cardiomyopathy [ICD-11: BC43]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[8]
Target Regulator	5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)		Protein coding	Regulator Info
Responsed Drug	Salidroside		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male C57/BL mice (aged between 6 and 8 weeks and weighing 20 ± 2 g) were randomly divided into 6 groups (n = 6 mice per group) with equal number of mice in each group. The groups included saline control group (control group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days; DOX model group (DOX group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days and a single intraperitoneal administration of 10 mgxkg-1 DOX (HY-15,142, MCE, China) to the mice on the seventh day. Click to Show/Hide
Response regulation	Salidroside markedly down-regulated ferroptotic cell death by activating AMPK-dependent signaling pathways including regulating abnormal fatty acid metabolism and maintaining mitochondrial function. Therefore, salidroside is can be exploited to develop a novel medication for clinical Doxorubicin-induced cardiotoxicity.

Ascorbic Acid [Approved]

Drug Info

In total 2 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	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.
Experiment 2 Reporting the Ferroptosis-centered Drug Response				[2]
Drug for Ferroptosis	Inducer
Response Target	Heme oxygenase 1 (HMOX1)		Driver; Suppressor	Target Info
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm³, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. Click to Show/Hide
Response regulation	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.

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	Phospholipid hydroperoxide glutathione peroxidase (GPX4)		Suppressor	Target Info
Responsed Disease	Intracerebral hemorrhage		ICD-11: 8B00	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
In Vivo Model	Rats were anaesthetised through intraperitoneal injection of pentobarbital (40 mg/kg) and placed onto a stereotaxic instrument (RWD Life Science Co., Ltd.). A 1-cm midline incision was performed in the rat scalp to expose the intersection point. Then, a hole 3.2 mm lateral and 1.4 mm anterior to the right bregma was produced. Next, 1.0 ul collagenase type IV (0.25 IU/ul; C5138; Sigma-Aldrich, USA) was injected into the basal ganglia via a microinjection pump (4.2 mm depth below the endocranium) at a rate of 0.2 ul/min. The needle was maintained for 5 min after injection to prevent backflow. Thereafter, the skin incision was closed using sutures. Rats in the sham group received 1.0 ul saline instead of collagenase type IV. Click to Show/Hide
Response regulation	Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway

Fingolimod [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[4]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
Responsed Disease	Multiple myeloma		ICD-11: 2A83	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
Response regulation	Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.

zero-valent-iron nanoparticle [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[3]
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
	mTOR signaling pathway			hsa04150
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A9 cells	Lung carcinoma	Mus musculus	CVCL_S007
	MRC-5 cells	Normal	Homo sapiens	CVCL_0440
	IMR-90 cells	Normal	Homo sapiens	CVCL_0347
In Vivo Model	5-6-week-old BALB/c nude mice (ZVI@Ag treatment) or NOD/SCID mice (ZVI@CMC treatment) were subcutaneously implanted with 1 x 10⁶ H460 cells. For A549 xenograft model of immunodeficient mouse and spontaneous lung metastasis model, 5-6-week-old NOD/SCID mice were subcutaneously implanted with 5 x 10⁶ A549 cells. For experimental lung metastasis model, H460 cells (1 x 10⁶ cells/200 uL) were resuspended in serum-free medium and injected intravenously (i.v.) into tail-vein of NOD/SCID mice. For subcutaneous model of immunocompetent mouse, LLC cells (5 x 10⁵) were injected into both flank of 6-week-old C57BL/6 mice. Click to Show/Hide
Response regulation	Zero-valent-iron nanoparticle (ZVI-NP) triggered ferroptosis selectively in lung cancer cells by suppressing NRF2-mediated cytoprotection program, which was attributed to the ZVI-NP-induced disruption of PRKAA1 (AMPK)/mTOR signaling and activation of GSK3/-TrCP-dependent degradation system.

Amentoflavone [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[7]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Corpus uteri cancer		ICD-11: 2C76	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hESCs (Human endometrial stromal cells)
	KLE cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
Response regulation	Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.

Dihydroartemisinin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[5]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell proliferation
	Cell cycle
In Vitro Model	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	KG1 cells	Normal	Mus musculus	CVCL_UD72
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In Vivo Model	BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 10⁷, suspended in 0.1 mL PBS). After tumors reached 100-200 mm³, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper. Click to Show/Hide
Response regulation	Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death.

Salidroside [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[8]
Drug for Ferroptosis	Suppressor
Response Target	Unspecific Target
Responsed Disease	Cardiomyopathy		ICD-11: BC43	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male C57/BL mice (aged between 6 and 8 weeks and weighing 20 ± 2 g) were randomly divided into 6 groups (n = 6 mice per group) with equal number of mice in each group. The groups included saline control group (control group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days; DOX model group (DOX group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days and a single intraperitoneal administration of 10 mgxkg-1 DOX (HY-15,142, MCE, China) to the mice on the seventh day. Click to Show/Hide
Response regulation	Salidroside markedly down-regulated ferroptotic cell death by activating AMPK-dependent signaling pathways including regulating abnormal fatty acid metabolism and maintaining mitochondrial function. Therefore, salidroside is can be exploited to develop a novel medication for clinical Doxorubicin-induced cardiotoxicity.

Typhaneoside [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[6]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
	AMPK signaling pathway			hsa04152
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell autophagy
In Vitro Model	KAS-6/1 cells	Plasma cell myeloma	Homo sapiens	CVCL_9544
	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	NB4 cells	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	4-week-old BALB/c malenude mice(Peking University Health Science Center, Beijing, China) were subcutaneously injection with HL60 cells (1 x 10⁷). After tumor volume reached 50 mm³, mice were randomly divided into 4 groups (n = 16/group). TYP was administered intraperitoneal injection once a day at 10, 20 and 30 mg/kg body weight and the mice in normal control group were received equal amounts of 10% DMSO in sterile corn oil. Click to Show/Hide
Response regulation	Typhaneoside (TYP) significantly triggered autophagy in acute myeloid leukemia (AML) cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately.

References

Ref 1	Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway. Basic Clin Pharmacol Toxicol. 2023 May;132(5):369-383. doi: 10.1111/bcpt.13848. Epub 2023 Mar 7.
Ref 2	Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway. Oxid Med Cell Longev. 2022 Jul 19;2022:5361241. doi: 10.1155/2022/5361241. eCollection 2022.
Ref 3	An innovative NRF2 nano-modulator induces lung cancer ferroptosis and elicits an immunostimulatory tumor microenvironment. Theranostics. 2021 May 13;11(14):7072-7091. doi: 10.7150/thno.57803. eCollection 2021.
Ref 4	FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells. Life Sci. 2020 Nov 1;260:118077. doi: 10.1016/j.lfs.2020.118077. Epub 2020 Aug 15.
Ref 5	DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med. 2019 Feb 1;131:356-369. doi: 10.1016/j.freeradbiomed.2018.12.011. Epub 2018 Dec 14.
Ref 6	Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy. Biochem Biophys Res Commun. 2019 Sep 3;516(4):1265-1271. doi: 10.1016/j.bbrc.2019.06.070. Epub 2019 Jul 10.
Ref 7	Amentoflavone promotes ferroptosis by regulating reactive oxygen species (ROS) /5'AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) to inhibit the malignant progression of endometrial carcinoma cells. Bioengineered. 2022 May;13(5):13269-13279. doi: 10.1080/21655979.2022.2079256.
Ref 8	Salidroside inhibits doxorubicin-induced cardiomyopathy by modulating a ferroptosis-dependent pathway. Phytomedicine. 2022 Jan 29;99:153964. doi: 10.1016/j.phymed.2022.153964. Online ahead of print.

Ferroptosis Regulator Information

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Correspondence

Prof. Shuiping Liu