Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00011)
Name |
Acute myeloid leukaemia
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ICD |
ICD-11: 2A60
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Full List of Target(s) of This Ferroptosis-centered Disease
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | GSK3368715 | Phase 1 | |||
Responsed Regulator | Protein arginine N-methyltransferase 1 (PRMT1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
HEL cells | Erythroleukemia | Homo sapiens | CVCL_0001 | ||
MOLM-13 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day.
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Response regulation | Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. | ||||
Unspecific Target
In total 7 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | Dihydroartemisinin | Investigative | |||
Responsed Regulator | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) | Driver | |||
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 Disease Response by This Target | [3] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | Dihydroartemisinin | Investigative | |||
Responsed Regulator | Metallothionein-1A (MT1A) | . | |||
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 Disease Response by This Target | [4] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | Typhaneoside | Investigative | |||
Responsed Regulator | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) | Driver | |||
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.
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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 4 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | Basic helix-loop-helix ARNT-like protein 1 (BMAL1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | MOLM-13 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | |
Response regulation | ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in acute myeloid leukemia (AML) cells. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [14] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | CircKDM4C (circRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | hBMSCs (Bone marrow stromal cells) | ||||
K-562 cells | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | ||
MOLM-13 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | ||
In Vivo Model |
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.
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Response regulation | The overexpression of circKDM4C in AML cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to acute myeloid leukemia (AML) patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [14] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | hsa-let-7b-5p (miRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | hBMSCs (Bone marrow stromal cells) | ||||
K-562 cells | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | ||
MOLM-13 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | ||
In Vivo Model |
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.
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Response regulation | The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [14] | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | hBMSCs (Bone marrow stromal cells) | ||||
K-562 cells | Chronic myelogenous leukemia | Homo sapiens | CVCL_0004 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | ||
MOLM-13 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_2119 | ||
In Vivo Model |
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.
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Response regulation | The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 4 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | Perillaldehyde | Investigative | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | Jurkat cells | T acute lymphoblastic leukemia | Homo sapiens | CVCL_0065 | |
DLD-1 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0248 | ||
SH-SY5Y cells | Neuroblastoma | Homo sapiens | CVCL_0019 | ||
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | ||
Response regulation | We investigated and characterized its antileukemic potential in vitro, disclosing its ability to trigger ferroptosis. Specifically, perillaldehyde induced lipid peroxidation, decreased glutathione peroxidase 4 protein expression, and depleted intracellular glutathione on HL-60 promyelocytic leukemia cells. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | APR-246 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
MOLM-14 cells | Leukemia | Homo sapiens | CVCL_7916 | ||
SET-2 cells | Acute megakaryoblastic leukemia | Homo sapiens | CVCL_2187 | ||
MV4-11 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | ||
OCI-AML-2 cells | Acute myeloid leukemia | Homo sapiens | CVCL_1619 | ||
OCI-AML3 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_1844 | ||
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 | ||
In Vivo Model |
Xenograft tumors were generated by randomly injecting 1 x 106 MOLM14 shCTRL or shSLC7A11 cells into the tail veins of NOD/SCID IL-2 receptor g-chain-null mice (NSG) aged 6-9 weeks. Fourteen days after injection, doxycycline (200 mg/mL) and sucrose (1% weight:volume) were added to the drinking water of these animals. After 3 days, the mice were randomly treated with a daily intraperitoneal injection of APR-246 (100 mg/kg) or vehicle (phosphate-buffered saline [PBS]) for 4 days.
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Response regulation | APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | Sulforaphane | Investigative | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Fatty acid metabolism | hsa01212 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell apoptosis | |||||
In Vitro Model | U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
MV4-11 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 | ||
Response regulation | Sulforaphane triggers different types of PCD in a concentration-dependent manner on the two tested acute myeloid leukemia cell lines. Deepening the molecular mechanisms on U-937 cells, we discovered that at lower concentrations, SFN induces apoptosis; at higher concentrations, SFN elicits ferroptosis, characterized by the depletion of intracellular GSH, the downregulation of GPX4 protein expression, and lipid peroxidation. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | Aldehyde dehydrogenase family 3 member A2 (ALDH3A2) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
MOLM-14 cells | Leukemia | Homo sapiens | CVCL_7916 | ||
Mono-Mac-6 cells | Acute monocytic leukemia | Homo sapiens | CVCL_1426 | ||
NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | ||
NOMO-1 cells | Acute monocytic leukemia | Homo sapiens | CVCL_1609 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
In Vivo Model |
Six- to 12-week-old Aldh-mut and Aldh-Ctrl mice were used to generate MLL-AF9 leukemia through retroviral transduction. This was transplanted into lethally irradiated (9 Gy) primary leukemic C57BL/6J mice and then into sublethally irradiated (4.5 Gy) secondary leukemic C57BL/6J mice. Forty-eight hours after injection into secondary recipients, these mice received 3 doses of polyinosinic-polycytidylic acid (GE Healthcare) on alternate days.
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Response regulation | Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects acute myeloid leukemia cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Drug | All-trans retinoic acid derivative | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | |
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
In Vivo Model |
Six- to seven-week-old female NCG mice were obtained from the Nanjing model animal research institute (Nanjing, China). Mice were raised in individually ventilated cages of Anhui Medical University (Hefei, China). Then, an injection of NB4 cells (5 x 106/100 ul) suspended in chilled Matrigel and PBS (1:1) was given into the right flank of each mouse. For each experiment, the animals (n = 12) were randomly allocated into the two groups and treated with solvent or 10 mg/kg ATPR (intraperitoneal injection, once every other day) for 7 days.
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Response regulation | ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). ATPR-induced ferroptosis was regulated by autophagy via iron homeostasis, especially Nrf2. | ||||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
Responsed Drug | Honokiol | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model | THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
SKM-1 cells | Acute myeloid leukemia | Homo sapiens | CVCL_0098 | |
Response regulation | Honokiol decreased the viability of the targeted Acute myeloid leukemia cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. And HMOX1 was a critical target in honokiol-induced ferroptosis. | |||
Ferritin heavy chain (FTH1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | ||||
Responsed Regulator | Iron-sulfur cluster assembly enzyme ISCU (ISCU) | Suppressor | |||
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. ISCU over-expression robustly alleviated the iron starvation response through regulating the expression of IRPs and downstream FTH. ISCU significantly attenuated DHA induced ferroptosis by regulating iron metabolism, rescuing the mitochondrial function and increasing the level of GSH. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 2 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Childhood acute monocytic leukemia [ICD-11: 2A60] | |||
Responsed Drug | Indole-3-pyruvic acid | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 |
MLL/AF4+ RS4 cells | Adult B acute lymphoblastic leukemia | Homo sapiens | CVCL_0093 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | |
NIH3T3 cells | Normal | Mus musculus | CVCL_0594 | |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | |
Response regulation | Indole-3-pyruvate (I3P) suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program in Childhood acute monocytic leukemia. And I3P elevated the activation of compensatory gene expression as indicated by increased protein amounts of SLC7A11 and HO-1, two important target genes of anti-oxidative stress pathways. | |||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
Responsed Regulator | Lysine-specific demethylase 3B (KDM3B) | Suppressor | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model | HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 |
HEK293 cells | Normal | Homo sapiens | CVCL_0045 | |
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
Response regulation | Since KDM3B has been shown to associate with acute myeloid leukemia (AML). KDM3B protects cells from Erastininduced ferroptosis through transcriptional upregulation of SLC7A11 via interaction with ATF4. | |||
References