Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00012)
Name |
Diffuse large B-cell lymphoma
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ICD |
ICD-11: 2A81
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Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Responsed Disease | Diffuse large B-cell lymphoma [ICD-11: 2A81] | ||||
Responsed Drug | Dimethyl fumarate | Approved | |||
Responsed Regulator | Signal transducer and activator of transcription 3 (STAT3) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | A-431 cells | Skin squamous cell carcinoma | Homo sapiens | CVCL_0037 | |
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
HaCaT cells | Normal | Homo sapiens | CVCL_0038 | ||
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | ||
Huh-7 cells | Hepatocellular carcinoma | Homo sapiens | CVCL_0336 | ||
SK-MEL-28 cells | Cutaneous melanoma | Homo sapiens | CVCL_0526 | ||
SMMC-7721 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0534 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
For the VFN-D1 patient-derived and the HBL-1 xenograft mouse models, adult female NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were implanted subcutaneously with 1 x 107 cells in PBS (300 ul). Once mice developed palpable tumors, the animals were randomized into control, DMF (daily i.p. treatment with 500 ul of 3 mg/ml DMF in PBS), ABT-199 (daily p.o. treatment with 100 mg/kg in ethanol/PhosalG/PEG400) or DMF+ABT-199 treated groups.
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Response regulation | Dimethyl fumarate (DMF) induces lipid peroxidation and thus ferroptosis, particularly in GCB diffuse large B-cell lymphoma (DLBCL). In ABC DLBCL cells, which are addicted to NF-kB and STAT3 survival signaling, DMF treatment efficiently inhibits the activity of the IKK complex and Janus kinases . | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Responsed Disease | Diffuse large B-cell lymphoma [ICD-11: 2A81] | ||||
Responsed Drug | Artesunate | Investigative | |||
Responsed Regulator | Signal transducer and activator of transcription 3 (STAT3) | Suppressor | |||
Pathway Response | JAK-STAT signaling pathway | hsa04630 | |||
Ferroptosis | hsa04216 | ||||
Autophagy | hsa04140 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
In Vitro Model | U-2932 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1896 | |
SU-DHL-2 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_9550 | ||
SU-DHL-4 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_0539 | ||
SU-DHL-6 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_2206 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
Female NOD/SCID mice (age, 6 weeks; body weight, 20 ± 2 g) were purchased from Beijing Huafukang Biotechnology Co., Ltd., maintained under pathogen-free conditions and allowed free access to sterilized food and water. After a week of adaptation to their surroundings, 1 x 107 U2932 cells were subcutaneously injected into the right flank near the hind leg of each mouse. Following the growth of palpable tumors (tumor volume of 50-100 mm3), the mice were randomly divided into two groups (n = 5 mice/group) and treated with 100 ul normal saline (NS) or ART (120 mg/kg/day) via intraperitoneal injection.
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Response regulation | Artesunate (ART) was found to exert its effects via inhibition of STAT3 activation. ART may induce apoptosis and cell cycle arrest to inhibit cell proliferation, and regulate autophagy and ferroptosis via impairing the STAT3 signaling pathway in diffuse large B cell lymphoma (DLBCL) cells. | ||||
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Target for Ferroptosis | Marker/Suppressor/Driver | ||||
Responsed Disease | Diffuse large B-cell lymphoma [ICD-11: 2A81] | ||||
Responsed Regulator | Histone-lysine N-methyltransferase EZH2 (EZH2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | Karpas-422 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1325 | |
U-2932 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1896 | ||
WILL-2 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1901 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
All animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai Institute of Materia Medica and performed in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care. Tumors were measured twice weekly and volumes were calculated using the formula TV=length x width2 x 1/2.
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Response regulation | EZH2 inhibition upregulated-TfR-1 dysregulation leads to drug resistance in EZH2 WT diffuse large B-cell lymphoma (DLBCL). On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Diffuse large B-cell lymphoma [ICD-11: 2A81] | ||||
Responsed Regulator | Histone-lysine N-methyltransferase EZH2 (EZH2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | Karpas-422 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1325 | |
U-2932 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1896 | ||
WILL-2 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1901 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
All animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai Institute of Materia Medica and performed in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care. Tumors were measured twice weekly and volumes were calculated using the formula TV=length x width2 x 1/2.
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Response regulation | EZH2 inhibition upregulated-TfR-1 dysregulation leads to drug resistance in EZH2 WT diffuse large B-cell lymphoma (DLBCL). On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Diffuse large B-cell lymphoma [ICD-11: 2A81] | ||||
Responsed Drug | Imidazole ketone erastin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SU-DHL-1 cells | Anaplastic large cell lymphoma | Homo sapiens | CVCL_0538 | |
SU-DHL-2 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_9550 | ||
SU-DHL-6 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_2206 | ||
SU-DHL-8 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_2207 | ||
SU-DHL-10 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1889 | ||
SU-DHL-16 cells | B-cell non-Hodgkin lymphoma | Homo sapiens | CVCL_1890 | ||
A3/Kawakami cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1062 | ||
OCI-LY8 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_8803 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
DoHH2 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1179 | ||
HBL-1 cells | Non-Hodgkin lymphoma | Homo sapiens | CVCL_M572 | ||
U-2932 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1896 | ||
SU-DHL-7 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_4380 | ||
SU-DHL-9 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_4379 | ||
A4/Fukuda cells | B acute lymphoblastic leukemia | Homo sapiens | CVCL_1064 | ||
WSU-NHL cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1793 | ||
SU-DHL-5 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1735 | ||
Karpas-422 cells | Diffuse large B-cell lymphoma | Homo sapiens | CVCL_1325 | ||
In Vivo Model |
NOD/SCID mice (12-weeks of age and ~28 g weight) were weighed before injection and divided into groups of 3 mice per cage. Mice were dosed using three different routes, IP and PO with 50 mg/kg IKE, and IV with 17 mg/kg IKE. Samples were collected at 0, 1, 3, 4, and 8 h from three mice per time point. Additionally, three mice per group were used as controls by administration with equivalent amount of vehicle 1 by IP, PO, and IV, and samples were collected at 8 h. At the appropriate time, mice were sacrificed by CO2 asphyxiation for 3 min and ~0.5 mL of blood was collected via cardiac puncture.
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Response regulation | Imidazole ketone erastin (IKE) is a potent, selective, and metabolically stable system xc- (SLC7A11)inhibitor. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model. | ||||
References