Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00021)
Name |
Gastrointestinal cancer
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ICD |
ICD-11: 2B5B
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Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastrointestinal cancer [ICD-11: 2B5B] | ||||
Responsed Drug | Berberine | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
In Vitro Model | HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | |
TMK-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_4384 | ||
CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | ||
In Vivo Model |
Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day.
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Response regulation | Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the GIC and suppressing stemness. BBR induces cell death in gastrointestinal cancer cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Upper gastrointestinal adenocarcinoma [ICD-11: 2B5B] | ||||
Responsed Regulator | Aurora kinase A (AURKA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | OE33 cells | Barrett adenocarcinoma | Homo sapiens | CVCL_0471 | |
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
STKM-2 cells | Gastric carcinoma | Homo sapiens | CVCL_M570 | ||
Response regulation | Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Upper gastrointestinal adenocarcinoma [ICD-11: 2B5B] | ||||
Responsed Regulator | hsa-miR-4715-3p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | OE33 cells | Barrett adenocarcinoma | Homo sapiens | CVCL_0471 | |
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
STKM-2 cells | Gastric carcinoma | Homo sapiens | CVCL_M570 | ||
Response regulation | Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis. | ||||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
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 | Gastrointestinal cancer [ICD-11: 2B5B] | ||||
Responsed Drug | Berberine | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
In Vitro Model | HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | |
TMK-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_4384 | ||
CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | ||
In Vivo Model |
Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day.
Click to Show/Hide
|
||||
Response regulation | Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the GIC and suppressing stemness. BBR induces cell death in gastrointestinal cancer cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastrointestinal cancer [ICD-11: 2B5B] | ||||
Responsed Drug | Berberine | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
In Vitro Model | HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | |
TMK-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_4384 | ||
CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | ||
In Vivo Model |
Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day.
Click to Show/Hide
|
||||
Response regulation | Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the gastrointestinal cancer and suppressing stemness. BBR induces cell death in GIC cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. | ||||
References