Ferroptosis Regulator Information
General Information of the Ferroptosis Regulator (ID: REG10038)
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
BRD4
can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
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Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Ferritin heavy chain (FTH1) [Suppressor; Marker]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
4F2 cell-surface antigen heavy chain (SLC3A2) [Suppressor]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [2] | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Responsed Drug | I-BET151 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
SK-BR-3 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0033 | ||
In Vivo Model |
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.
Click to Show/Hide
|
||||
Response regulation | BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. | ||||
Experiment 2 Reporting the Ferroptosis Target of This Regulator | [3] | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
HCC38 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1267 | ||
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
HCC1143 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1245 | ||
HCC1937 cells | Breast ductal carcinoma | Homo sapiens | CVCL_0290 | ||
HCC70 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1270 | ||
HCC38 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1267 | ||
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | ||
BT-549 cells | Invasive breast carcinoma | Homo sapiens | CVCL_1092 | ||
SUM159 cells | Breast pleomorphic carcinoma | Homo sapiens | CVCL_5423 | ||
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
In Vivo Model |
For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination.
Click to Show/Hide
|
||||
Response regulation | BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET (BRD2, BRD3, BRD4, BRDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. | ||||
Breast cancer [ICD-11: 2C60]
In total 6 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Responsed Drug | JQ1 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response | [2] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Responsed Drug | I-BET151 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
SK-BR-3 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0033 | ||
In Vivo Model |
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.
Click to Show/Hide
|
||||
Response regulation | BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response | [3] | ||||
Target Regulator | Bromodomain-containing protein 4 (BRD4) | Protein coding | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
HCC38 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1267 | ||
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
HCC1143 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1245 | ||
HCC1937 cells | Breast ductal carcinoma | Homo sapiens | CVCL_0290 | ||
HCC70 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1270 | ||
HCC38 cells | Breast ductal carcinoma | Homo sapiens | CVCL_1267 | ||
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | ||
BT-549 cells | Invasive breast carcinoma | Homo sapiens | CVCL_1092 | ||
SUM159 cells | Breast pleomorphic carcinoma | Homo sapiens | CVCL_5423 | ||
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
In Vivo Model |
For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination.
Click to Show/Hide
|
||||
Response regulation | BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET (BRD2, BRD3, BRD4, BRDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. | ||||
JQ1
[Investigative]
In total 4 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 2 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Ferritin heavy chain (FTH1) | Suppressor; Marker | |||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
|
||||
Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 3 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Cystine/glutamate transporter (SLC7A11) | Driver; Suppressor | |||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
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Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
Experiment 4 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | 4F2 cell-surface antigen heavy chain (SLC3A2) | Suppressor | |||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Hs-578T cells | Invasive breast carcinoma | Homo sapiens | CVCL_0332 | ||
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
MCF-10A cells | Normal | Homo sapiens | CVCL_0598 | ||
In Vivo Model |
Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days.
Click to Show/Hide
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Response regulation | Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. | ||||
I-BET151
[Investigative]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [2] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Unspecific Target | ||||
Responsed Disease | Breast cancer | ICD-11: 2C60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
SK-BR-3 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0033 | ||
In Vivo Model |
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.
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Response regulation | BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. | ||||
References