General Information of the Ferroptosis Target (ID: TAR10044)
Target Name Natural resistance-associated macrophage protein 2 (SLC11A2)
Synonyms
Divalent cation transporter 1; Divalent metal transporter 1; Solute carrier family 11 member 2
    Click to Show/Hide
Gene Name SLC11A2
Sequence
MVLGPEQKMSDDSVSGDHGESASLGNINPAYSNPSLSQSPGDSEEYFATYFNEKISIPEE
EYSCFSFRKLWAFTGPGFLMSIAYLDPGNIESDLQSGAVAGFKLLWILLLATLVGLLLQR
LAARLGVVTGLHLAEVCHRQYPKVPRVILWLMVELAIIGSDMQEVIGSAIAINLLSVGRI
PLWGGVLITIADTFVFLFLDKYGLRKLEAFFGFLITIMALTFGYEYVTVKPSQSQVLKGM
FVPSCSGCRTPQIEQAVGIVGAVIMPHNMYLHSALVKSRQVNRNNKQEVREANKYFFIES
CIALFVSFIINVFVVSVFAEAFFGKTNEQVVEVCTNTSSPHAGLFPKDNSTLAVDIYKGG
VVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVVLTRSIAI
IPTLLVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSDFANGLGWRIAG
GILVLIICSINMYFVVVYVRDLGHVALYVVAAVVSVAYLGFVFYLGWQCLIALGMSFLDC
GHTCHLGLTAQPELYLLNTMDADSLVSR

    Click to Show/Hide
Family NRAMP family
Function
Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1. Selectively transports various divalent metal cations, in decreasing affinity: Cd(2+) > Fe(2+) > Co(2+), Mn(2+) >> Zn(2+), Ni(2+), VO(2+). Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe(2+) and TF-associated endosomal Fe(2+) transport in erythroid precursors and other cells. Enables Fe(2+) and Mn(2+) ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense. Can mediate uncoupled fluxes of either protons or metal ions.

    Click to Show/Hide
Gene ID 4891
Uniprot ID
P49281
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
SLC11A2 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
Mitogen-activated protein kinase 14 (MAPK14)
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Drug Artesunate Investigative
Pathway Response MAPK signaling pathway hsa04010
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days.

    Click to Show/Hide
Response Description Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4.
mmu-miR-375-3p (miRNA)
Ulcerative colitis [ICD-11: DD71]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
hCCs (Colon cells)
In Vivo Model
Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed.

    Click to Show/Hide
Response Description IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and ulcerative colitis progression in DSS-treated mice.
Metalloreductase STEAP3 (STEAP3)
Ischemia/reperfusion injury [ICD-11: DB98]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
rBMMSCs (Rat bone marrow mesenchymal stem cells)
IAR 20 cells Normal Homo sapiens CVCL_5296
Response Description MiR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft ischemia reperfusion injury. And HUCB-MSCs-exos inhibited the expression of DMT1 by delivering miR-23a-3p, which suppressed cardiomyocyte ferroptosis after myocardial infarction.
Interferon regulatory factor 7 (IRF7)
Ulcerative colitis [ICD-11: DD71]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
hCCs (Colon cells)
In Vivo Model
Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed.

    Click to Show/Hide
Response Description IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and ulcerative colitis progression in DSS-treated mice.
hsa-miR-23a-3p (miRNA)
Acute myocardial infarction [ICD-11: BA41]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [4]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hUCB-MSCs (Human umbilical cord blood derived mesenchymal stem cells)
In Vivo Model
A total of 72 C57BL/6J mice (six animals per group) were obtained from the Shanghai Laboratory Animals Center. The mouse model of AMI was performed by permanent ligation of the LAD coronary artery. PBS or exosomes (5 ug, in 20 ul PBS) was injected into the border zone of infarcted heart at three sites.

    Click to Show/Hide
Response Description The exosome of MSCs derived from human umbilical cord blood (HUCB-MSC) has been reported to have cardioprotective effects on mouse models of acute myocardial infarction (AMI) and cardiomyocyte hypoxia injury. HUCB-MSCs-exosomes may suppress DMT1 expression by miR-23a-3p to inhibit ferroptosis and attenuate myocardial injury.
hsa-miR-124-3p (miRNA)
Ischemia/reperfusion injury [ICD-11: DB98]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
rBMMSCs (Rat bone marrow mesenchymal stem cells)
IAR 20 cells Normal Homo sapiens CVCL_5296
Response Description MiR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft ischemia reperfusion injury. And HUCB-MSCs-exos inhibited the expression of DMT1 by delivering miR-23a-3p, which suppressed cardiomyocyte ferroptosis after myocardial infarction.
hsa-miR-10a-5p (miRNA)
Intervertebral disc degeneration [ICD-11: FA80]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [5]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hCDs (Chondrocytes)
Response Description Inflammatory cytokine IL-6 appeared in Intervertebral disc degeneration (IDD) aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. The ferroptosis-inhibitory effect exhibited by overexpressing miR-10a-5p was achieved by promoting GPX4 and ferroportin-1 (FPN1) but suppressing divalent metal transporter 1 (DMT1) expression in IL-6-treated cartilage cells.
Unspecific Regulator
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [6]
Responsed Drug Temozolomide Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
TG905 (Human glioblastoma cells)
Response Description Temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells. The results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway.
Osteosarcoma [ICD-11: 2B51]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [7]
Responsed Drug Bavachin Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
HOS cells Osteosarcoma Homo sapiens CVCL_0312
Response Description Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 (SLC11A2) expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [8]
Responsed Drug Sulfasalazine Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Response Description Sulfasalazine (SAS) upregulated TFRC and DMT1. Knockdown of the ER increased TFRC expression in breast cancer cells. In conclusion SAS could trigger ferroptosis in breast cancer cells, especially in cells with low ER expression.
Parkinson disease [ICD-11: 8A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [9]
Responsed Drug Epigallocatechin Gallate Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Response Description Epigallocatechin-3-Gallate (EGCG) pretreatment counteracted 6-OHDA-induced increased expression of divalent metal transporter-1 (DMT1) and hepcidin and decreased expression of the iron-export protein ferroportin 1 (Fpn1), leading to a 28% reduction in Fe2+ uptake. EGCG inhibits iron overload, decreased LPO, and increased GSH levels in Parkinson disease models, which are the three major hallmarks of ferroptosis.
Temporal lobe epilepsy [ICD-11: 8A61]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [10]
Responsed Drug Klotho Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
rHTs (Rat hippocampal tissues)
In Vivo Model
Adult male Sprague-Dawley (SD) rats aged between 6 and 8 weeks old and weighing between 280 and 320 g were purchased from Hunan slake jingda laboratory animal company (Changsha, China) and used in this study. Under a 12 h light/dark cycle, rats had free access to water and food and were maintained in a room with controlled temperature, humidity. These rats were adapted to the environment for at least 2 week before we began to enter the experimental procedure.

    Click to Show/Hide
Response Description Klotho overexpression inhibits ferroptosis in temporal lobe epilepsy (TLE) with cognitive deficits and has a neuroprotective effect. Moreover, for the first time, we found that klotho overexpression inhibits ferroptosis and iron overload in TLE with cognitive deficits. In addition, klotho overexpression down-regulated the expression of DMT1 and up-regulated FPN expression which regulated iron metabolism balance.
Cerebral ischemia [ICD-11: 8B10]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [11]
Responsed Drug Naotaifang Extract Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hBCs (Brain cells)
In Vivo Model
Specific pathogen-free adult male SD rats, (80 ± 5) days old and weighing 220-250 g, were provided by the Hunan Slack Jingda Experimental Animal Co., Ltd (Hunan, China). SD rats were randomly divided into 4 groups with 15 in each group: sham operation group, MCAO group, MCAO + DFP group and MCAO + NTE group. The rats were treated with drugs via oral gavage. According to the average body weight, the MCAO + NTE rats were given NTE at 27 g/kg, and the sham operation and the MCAO rats were given the same volume of saline (2.5 mL) for 7 consecutive days. The MCAO + DFP rats were given DFP at a dose of 125 mg/kg for 3 consecutive days.

    Click to Show/Hide
Response Description Acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with naotaifang extract involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.
Pulmonary fibrosis [ICD-11: CB03]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [12]
Responsed Drug Bleomycin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21.

    Click to Show/Hide
Response Description Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of TfR1 and DMT1 in a concentration- and time-dependent manner but similarly decreased those of FPN. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis.
Traumatic brain injury [ICD-11: NA07]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [13]
Responsed Drug Ebselen Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hBCs (Brain cells)
In Vivo Model
Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions.

    Click to Show/Hide
Response Description Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator [13]
Responsed Drug Hepcidin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hBCs (Brain cells)
In Vivo Model
Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions.

    Click to Show/Hide
Response Description Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen.
Mitogen-activated protein kinase 14 (MAPK14)
Artesunate [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Disease Glioblastoma [ICD-11: 2A00]
Pathway Response MAPK signaling pathway hsa04010
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days.

    Click to Show/Hide
Response Description Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4.
Unspecific Regulator
Temozolomide [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [6]
Responsed Disease Glioblastoma [ICD-11: 2A00]
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model TG905 (Human glioblastoma cells)
Response Description Temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells. The results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway.
Bavachin [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [7]
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
HOS cells Osteosarcoma Homo sapiens CVCL_0312
Response Description Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 (SLC11A2) expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.
Sulfasalazine [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [8]
Responsed Disease Breast cancer [ICD-11: 2C60]
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Response Description Sulfasalazine (SAS) upregulated TFRC and DMT1. Knockdown of the ER increased TFRC expression in breast cancer cells. In conclusion SAS could trigger ferroptosis in breast cancer cells, especially in cells with low ER expression.
Epigallocatechin Gallate [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [9]
Responsed Disease Parkinson disease [ICD-11: 8A00]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Response Description Epigallocatechin-3-Gallate (EGCG) pretreatment counteracted 6-OHDA-induced increased expression of divalent metal transporter-1 (DMT1) and hepcidin and decreased expression of the iron-export protein ferroportin 1 (Fpn1), leading to a 28% reduction in Fe2+ uptake. EGCG inhibits iron overload, decreased LPO, and increased GSH levels in Parkinson disease models, which are the three major hallmarks of ferroptosis.
Klotho [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [10]
Responsed Disease Temporal lobe epilepsy [ICD-11: 8A61]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Adult male Sprague-Dawley (SD) rats aged between 6 and 8 weeks old and weighing between 280 and 320 g were purchased from Hunan slake jingda laboratory animal company (Changsha, China) and used in this study. Under a 12 h light/dark cycle, rats had free access to water and food and were maintained in a room with controlled temperature, humidity. These rats were adapted to the environment for at least 2 week before we began to enter the experimental procedure.

    Click to Show/Hide
Response Description Klotho overexpression inhibits ferroptosis in temporal lobe epilepsy (TLE) with cognitive deficits and has a neuroprotective effect. Moreover, for the first time, we found that klotho overexpression inhibits ferroptosis and iron overload in TLE with cognitive deficits. In addition, klotho overexpression down-regulated the expression of DMT1 and up-regulated FPN expression which regulated iron metabolism balance.
Naotaifang Extract [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [11]
Responsed Disease Cerebral ischemia [ICD-11: 8B10]
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Specific pathogen-free adult male SD rats, (80 ± 5) days old and weighing 220-250 g, were provided by the Hunan Slack Jingda Experimental Animal Co., Ltd (Hunan, China). SD rats were randomly divided into 4 groups with 15 in each group: sham operation group, MCAO group, MCAO + DFP group and MCAO + NTE group. The rats were treated with drugs via oral gavage. According to the average body weight, the MCAO + NTE rats were given NTE at 27 g/kg, and the sham operation and the MCAO rats were given the same volume of saline (2.5 mL) for 7 consecutive days. The MCAO + DFP rats were given DFP at a dose of 125 mg/kg for 3 consecutive days.

    Click to Show/Hide
Response Description Acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with naotaifang extract involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.
Bleomycin [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [12]
Responsed Disease Pulmonary fibrosis [ICD-11: CB03]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21.

    Click to Show/Hide
Response Description Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of TfR1 and DMT1 in a concentration- and time-dependent manner but similarly decreased those of FPN. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis.
Ebselen [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [13]
Responsed Disease Traumatic brain injury [ICD-11: NA07]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions.

    Click to Show/Hide
Response Description Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen.
Hepcidin [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [13]
Responsed Disease Traumatic brain injury [ICD-11: NA07]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions.

    Click to Show/Hide
Response Description Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen.
References
Ref 1 Artesunate induces ferroptosis via modulation of p38 and ERK signaling pathway in glioblastoma cells. J Pharmacol Sci. 2022 Mar;148(3):300-306. doi: 10.1016/j.jphs.2022.01.007. Epub 2022 Jan 13.
Ref 2 Promotive role of IRF7 in ferroptosis of colonic epithelial cells in ulcerative colitis by the miR-375-3p/SLC11A2 axis. Biomol Biomed. 2023 May 1;23(3):437-449. doi: 10.17305/bjbms.2022.8081.
Ref 3 miR-124-3p delivered by exosomes from heme oxygenase-1 modified bone marrow mesenchymal stem cells inhibits ferroptosis to attenuate ischemia-reperfusion injury in steatotic grafts. J Nanobiotechnology. 2022 Apr 22;20(1):196. doi: 10.1186/s12951-022-01407-8.
Ref 4 Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice. Cell Biol Toxicol. 2021 Feb;37(1):51-64. doi: 10.1007/s10565-020-09530-8. Epub 2020 Jun 13.
Ref 5 Targeting miR-10a-5p/IL-6R axis for reducing IL-6-induced cartilage cell ferroptosis. Exp Mol Pathol. 2021 Feb;118:104570. doi: 10.1016/j.yexmp.2020.104570. Epub 2020 Nov 7.
Ref 6 Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells. Yonsei Med J. 2021 Sep;62(9):843-849. doi: 10.3349/ymj.2021.62.9.843.
Ref 7 Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells. Oxid Med Cell Longev. 2021 Oct 18;2021:1783485. doi: 10.1155/2021/1783485. eCollection 2021.
Ref 8 Sulfasalazineinduced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep. 2019 Aug;42(2):826-838. doi: 10.3892/or.2019.7189. Epub 2019 Jun 6.
Ref 9 Epigallocatechin-3-gallate: A phytochemical as a promising drug candidate for the treatment of Parkinson's disease. Front Pharmacol. 2022 Sep 12;13:977521. doi: 10.3389/fphar.2022.977521. eCollection 2022.
Ref 10 Klotho ameliorated cognitive deficits in a temporal lobe epilepsy rat model by inhibiting ferroptosis. Brain Res. 2021 Dec 1;1772:147668. doi: 10.1016/j.brainres.2021.147668. Epub 2021 Sep 27.
Ref 11 Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats. J Integr Med. 2020 Jul;18(4):344-350. doi: 10.1016/j.joim.2020.01.008. Epub 2020 Jan 21.
Ref 12 Iron deposition-induced ferroptosis in alveolar type II cells promotes the development of pulmonary fibrosis. Biochim Biophys Acta Mol Basis Dis. 2021 Dec 1;1867(12):166204. doi: 10.1016/j.bbadis.2021.166204. Epub 2021 Jun 24.
Ref 13 Hepcidin Promoted Ferroptosis through Iron Metabolism which Is Associated with DMT1 Signaling Activation in Early Brain Injury following Subarachnoid Hemorrhage. Oxid Med Cell Longev. 2021 Dec 27;2021:9800794. doi: 10.1155/2021/9800794. eCollection 2021.