General Information of the Disease (ID: DIS00027)
Name
Colon cancer
ICD
ICD-11: 2B90
Full List of Target(s) of This Ferroptosis-centered Disease
Ferroptosis suppressor protein 1 (AIFM2)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Drug NCS207895 Investigative
Responsed Regulator Protein Mdm4 (MDM4) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Response regulation Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Drug Nutlin-3 Investigative
Responsed Regulator E3 ubiquitin-protein ligase Mdm2 (MDM2) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Response regulation Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma.
Cystine/glutamate transporter (SLC7A11)
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Drug Sulfasalazine Investigative
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).

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Response regulation BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/ AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Drug Sulfasalazine Investigative
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).

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Response regulation BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Pt3R5G Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model RKO cells Colon carcinoma Homo sapiens CVCL_0504
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCM460 cells Normal Homo sapiens CVCL_0460
In Vivo Model
Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days.

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Response regulation Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer.
Unspecific Target
In total 8 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Albiziabioside A Investigative
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
hBMECs (Human brain microvascular endothelial cells)
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
HaCaT cells Normal Homo sapiens CVCL_0038
HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
CCD-841CoN cells Normal Homo sapiens CVCL_2871
BEAS-2B cells Normal Homo sapiens CVCL_0168
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
In Vivo Model
A total of 1 x 107 HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm3 (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection.

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Response regulation The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Ginkgo biflavones Investigative
Responsed Regulator E3 ubiquitin-protein ligase Mdm2 (MDM2) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
RKO cells Colon carcinoma Homo sapiens CVCL_0504
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
In Vivo Model
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).

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Response regulation Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Ginkgo biflavones Investigative
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
RKO cells Colon carcinoma Homo sapiens CVCL_0504
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
In Vivo Model
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).

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Response regulation Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [9]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Soyauxinium chloride Investigative
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Necroptosis hsa04217
Cell Process Cell ferroptosis
Cell apoptosis
Cell necroptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
CC531 cells Colon adenocarcinoma Rattus norvegicus CVCL_0206
Response regulation The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis in colon cancer.
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [10]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator Neutral ceramidase (ASAH2) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.

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Response regulation ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target [11]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator Cytoglobin (CYGB) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
Response regulation CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target [10]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.

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Response regulation ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target [11]
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
Response regulation CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Pt3R5G Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model RKO cells Colon carcinoma Homo sapiens CVCL_0504
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCM460 cells Normal Homo sapiens CVCL_0460
In Vivo Model
Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days.

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Response regulation Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer.
Stearoyl-CoA desaturase (SCD)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Target for Ferroptosis Suppressor
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator hsa-miR-423-5p (miRNA) Driver
Pathway Response Wnt signaling pathway hsa04310
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell stemness
In Vitro Model SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.

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Response regulation LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Target for Ferroptosis Suppressor
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Regulator LINC01606 (IncRNA) Suppressor
Pathway Response Wnt signaling pathway hsa04310
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
Cell stemness
In Vitro Model SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.

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Response regulation LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Target for Ferroptosis Suppressor
Responsed Disease Colon cancer [ICD-11: 2B90]
Responsed Drug Honokiol Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model SW48 cells Colon adenocarcinoma Homo sapiens CVCL_1724
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
LS174T cells Colon adenocarcinoma Homo sapiens CVCL_1384
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
RKO cells Colon carcinoma Homo sapiens CVCL_0504
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
In Vivo Model
Ten BALB/c nude mice (male, 4 weeks old, 18.0 ± 2.0 g) were randomly divided into two groups for the in vivo xenograft assay. Mice were injected with 5 x 106 RKO cells with stable overexpression GPX4 (described Lv-GPX4 group), control vector (described Lv-NC group). Cells were subcutaneously injected into the right anterior axilla of mice in both groups. Mice then received HNK (0.5 mg/kg/w) by intraperitoneal injection for 4 weeks. The subcutaneous tumor volumes in the nude mice in the two groups were recorded every two days.

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Response regulation Honokiol reduced the viability of Colon cancer (CC) cell lines by increasing ROS and Fe2+levels. HNK decreased the activity of Glutathione Peroxidase 4 (GPX4) but did not affect system Xc-. Thus, HNK can induce ferroptosis in CC cells by reducing the activity of GPX4.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
HIEC-6 cells Normal Homo sapiens CVCL_6C21
Response regulation RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4 in colon carcinoma cells, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Regulator Cyclin-dependent kinase inhibitor 1 (CDKN1A) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
HIEC-6 cells Normal Homo sapiens CVCL_6C21
Response regulation RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Regulator Ribonucleoside-diphosphate reductase large subunit (RRM1) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
HIEC-6 cells Normal Homo sapiens CVCL_6C21
Response regulation RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma.
Beclin-1 (BECN1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Colon carcinoma [ICD-11: 2B90]
Responsed Drug Sulfasalazine Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).

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Response regulation BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis in Colon cancer. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib).
References
Ref 1 MDM2 and MDMX promote ferroptosis by PPAR-mediated lipid remodeling. Genes Dev. 2020 Apr 1;34(7-8):526-543. doi: 10.1101/gad.334219.119. Epub 2020 Feb 20.
Ref 2 AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System X(c)(-) Activity. Curr Biol. 2018 Aug 6;28(15):2388-2399.e5. doi: 10.1016/j.cub.2018.05.094. Epub 2018 Jul 26.
Ref 3 Novel antitumor compound optimized from natural saponin Albiziabioside A induced caspase-dependent apoptosis and ferroptosis as a p53 activator through the mitochondrial pathway. Eur J Med Chem. 2018 Sep 5;157:759-772. doi: 10.1016/j.ejmech.2018.08.036. Epub 2018 Aug 14.
Ref 4 Ginkgo Biflavones Cause p53 Wild-Type Dependent Cell Death in a Transcription-Independent Manner of p53. J Nat Prod. 2023 Feb 24;86(2):346-356. doi: 10.1021/acs.jnatprod.2c00959. Epub 2023 Jan 26.
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