Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0226)
Name
Dihydroartemisinin
Synonyms
Dihydroartemisinin; 71939-50-9; Artenimol; Cotexin; Dihydroqinghaosu; Alaxin; Cotecxin; Dihydroartemisinine; 81496-82-4; Dynamax; Salaxin; Santecxin; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-ol; Di-hydroqinghaosu; GNF-PF-5634; Artenimol [INN]; Dihydro Artemisinin; (3r,5as,6r,8as,9r,10s,12r,12ar)-decahydro-3,6,9-trimethyl-3,12-epoxy-12h-pyrano[4,3-j][1,2]benzodioxepin-10-ol; .beta.-dihydroartemisinin; Dihydroartemisinin, .beta.-; 6A9O50735X; 3,12-Epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin-10-ol, decahydro-3,6,9-trimethyl-, (3R,5aS,6R,8aS,9R,10S,12R,12aR)-; 3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-ol, decahydro-3,6,9-trimethyl-, (3R,5aS,6R,8aS,9R,10S,12R,12aR)-; b-Dihydroartemisinin; ARTENIMOL [MART.]; ARTENIMOL [WHO-DD]; ARTENIMOL [WHO-IP]; DIHYDROARTEMISININ [MI]; GTPL9957; SCHEMBL17156483; CHEBI:135921; DTXSID501021652; ARTENIMOLUM [WHO-IP LATIN]; DIHYDROARTEMISININ [USP-RS]; DIHYDROARTEMISININ [WHO-DD]; HY-N0176; AKOS032949625; CS-5595; FT-0649320; EURARTESIM COMPONENT DIHYDROARTEMISININ; EN300-7419972; BRD-K62213621-001-01-6; (1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecan-10-ol; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-ol; (3R,5AS,6R,8AS,9R,10S,12R,12AR)-3,6,9-TRIMETHYLDECAHYDRO-3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN-10-OL

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Structure
Formula
C15H24O5
IUPAC Name
(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
Canonical SMILES
CC1CCC2C(C(OC3C24C1CCC(O3)(OO4)C)O)C
InChI
InChI=1S/C15H24O5/c1-8-4-5-11-9(2)12(16)17-13-15(11)10(8)6-7-14(3,18-13)19-20-15/h8-13,16H,4-7H2,1-3H3/t8-,9-,10+,11+,12+,13-,14-,15-/m1/s1
InChIKey
BJDCWCLMFKKGEE-ISOSDAIHSA-N
PubChem CID
3000518
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 7 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Endoplasmic reticulum chaperone BiP (HSPA5) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Specific pathogen-free athymic nude BALB/c mice (4-6 weeks old) were obtained from Guangdong Experimental Animal Centre (Guangzhou, China). To generate murine subcutaneous tumors, cells (for U251: 2 x 106 cells; for U373: 2 x 106 cells) were suspended in 0.2 ml PBS and injected into the flanks of mice (n = 6/group). Tumor volume was measured once every 3 days using calipers.

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Response regulation HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized Dihydroartemisinin-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Endoplasmic reticulum chaperone BiP (HSPA5) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Specific pathogen-free athymic nude BALB/c mice (4-6 weeks old) were obtained from Guangdong Experimental Animal Centre (Guangzhou, China). To generate murine subcutaneous tumors, cells (for U251: 2 x 106 cells; for U373: 2 x 106 cells) were suspended in 0.2 ml PBS and injected into the flanks of mice (n = 6/group). Tumor volume was measured once every 3 days using calipers.

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Response regulation HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized Dihydroartemisinin-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [6]
Target for Ferroptosis Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
A-172 cells Glioblastoma Homo sapiens CVCL_0131
Response regulation Dihydroartemisinin (DHA) had a selective killing effect on glioblastoma, which was associated with over-expression of transferrin receptors. The primary mechanism by which DHA caused ferroptosis was down-regulation of GPX4 and the following lipid ROS accumulation.
Experiment 4 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.

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Response regulation Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.
Experiment 5 Reporting the Ferroptosis-centered Drug Act on This Target [7]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell proliferation
Cell autophagy
In Vitro Model NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
In Vivo Model
GPX4 iKO H292 cells were inoculated by injecting 3 x 106 cells in 0.1 mL PBS subcutaneously in the right flank of six- to eight-week-old female athymic nude Foxn1nu/Foxn1 mice (Envigo, East Millstone, NJ, USA). Following inoculation, the mice were monitored until they have fully recovered and are moving. Mice were randomly allocated into their respective groups (non-blinded). Tumor growth was monitored regularly via external caliper measurements.

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Response regulation Dihydroartemisinin (DAT) can augment GPX4 inhibition-induced ferroptosis in a cohort of cancer cells that are otherwise highly resistant to ferroptosis. Collectively, artemisinin compounds can sensitize cells to ferroptosis by regulating cellular iron homeostasis in Lung mucoepidermoid carcinoma.
Experiment 6 Reporting the Ferroptosis-centered Drug Act on This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
Response regulation Dihydroartemisinin (DHA) treatment decreased the levels of GPX4, DHA significantly induced apoptosis and ferroptosis in a dose-dependent manner and exhibited high cellular toxicity on A549-GR (non-small cell lung cancer) cells when combined with gefitinib.
Experiment 7 Reporting the Ferroptosis-centered Drug Act on This Target [9]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Response regulation Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis.
Ferritin heavy chain (FTH1)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Marker
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Myc-associated zinc finger protein (MAZ) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.

    Click to Show/Hide
Response regulation Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Marker
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator TUG1 (IncRNA) Suppressor
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.

    Click to Show/Hide
Response regulation Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.
Unspecific Target
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator 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.

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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 Drug Act on This Target [4]
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Responsed Regulator Metallothionein-1A (MT1A) .
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model MOLM-14 cells Leukemia Homo sapiens CVCL_7916
OCI-AML-2 cells Acute myeloid leukemia Homo sapiens CVCL_1619
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
SET-2 cells Acute megakaryoblastic leukemia Homo sapiens CVCL_2187
MV4-11 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0064
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
UT-7/Epo cells Acute megakaryoblastic leukemia Homo sapiens CVCL_5202
SKM-1 cells Acute myeloid leukemia Homo sapiens CVCL_0098
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
Response regulation Dihydroartemisinin (DHA) activated zinc metabolism signaling, especially the upregulation of metallothionein (MT). DHA activates ferritinophagy and subsequent ferroptosis in AML and that MTs are involved in glutathione regenerating and antioxidant response in Acute Myeloid Leukemia.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [5]
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Panc02 cells Pancreatic ductal adenocarcinoma Mus musculus CVCL_D627
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In Vivo Model
Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 106 cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis.

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Response regulation Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression.
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [5]
Target for Ferroptosis Driver
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Panc02 cells Pancreatic ductal adenocarcinoma Mus musculus CVCL_D627
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In Vivo Model
Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 106 cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis.

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Response regulation Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression.
Nuclear receptor coactivator 4 (NCOA4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [9]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Response regulation Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis.
Heme oxygenase 1 (HMOX1)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Driver
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.

    Click to Show/Hide
Response regulation Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.
Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [10]
Target for Ferroptosis Marker/Driver
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
In Vivo Model
A total of 32 male BALB/c nude mice (age, 6-8 weeks; weight, 18-20 g) were obtained from HFK Bioscience Co. Ltd. and housed in a specific pathogen-free facility. The mice were randomly divided into four groups (n = 8/group) and PLC cells were subcutaneously injected into the nude mice. When the xenografted tumors had grown to 80-100 mm3, half of the mice in each group were administered with 100 mg/kg DHA for 5 days/week by gavage.

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Response regulation Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein responseinduced upregulation of CHAC1 expression. DHA also promoted the transcription of CHAC1.
References
Ref 1 Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells. J Exp Clin Cancer Res. 2019 Sep 13;38(1):402. doi: 10.1186/s13046-019-1413-7.
Ref 2 TUG1/MAZ/FTH1 Axis Attenuates the Antiglioma Effect of Dihydroartemisinin by Inhibiting Ferroptosis. Oxid Med Cell Longev. 2022 Sep 17;2022:7843863. doi: 10.1155/2022/7843863. eCollection 2022.
Ref 3 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 4 Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein. Cell Death Discov. 2023 Mar 17;9(1):97. doi: 10.1038/s41420-023-01371-8.
Ref 5 Dihydroartemisinin inhibits the growth of pancreatic cells by inducing ferroptosis and activating antitumor immunity. Eur J Pharmacol. 2022 Jul 5;926:175028. doi: 10.1016/j.ejphar.2022.175028. Epub 2022 May 13.
Ref 6 Dihydroartemisinin initiates ferroptosis in glioblastoma through GPX4 inhibition. Biosci Rep. 2020 Jun 26;40(6):BSR20193314. doi: 10.1042/BSR20193314.
Ref 7 Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis. Cell Death Differ. 2020 Jan;27(1):242-254. doi: 10.1038/s41418-019-0352-3. Epub 2019 May 21.
Ref 8 Dihydroartemisinin enhances gefitinib cytotoxicity against lung adenocarcinoma cells by inducing ROS-dependent apoptosis and ferroptosis. Kaohsiung J Med Sci. 2023 Jul;39(7):699-709. doi: 10.1002/kjm2.12684. Epub 2023 Apr 14.
Ref 9 Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis. Front Mol Biosci. 2023 Mar 31;10:1156062. doi: 10.3389/fmolb.2023.1156062. eCollection 2023.
Ref 10 Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein responseinduced upregulation of CHAC1 expression. Oncol Rep. 2021 Nov;46(5):240. doi: 10.3892/or.2021.8191. Epub 2021 Sep 24.