General Information of the Drug (ID: ferrodrug0432)
Name
Polyphyllin B
Drug Type
Small molecule
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Gastric cancer ICD-11: 2B72
Responsed Regulator Microtubule-associated proteins 1A/1B light chain 3B {ECO:0000305} (MAP1LC3B) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model NUGC-3 cells Gastric carcinoma Homo sapiens CVCL_1612
MKN-1 cells Gastric carcinoma Homo sapiens CVCL_1415
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
In Vivo Model
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.

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Response regulation We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy.
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Driver
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model NUGC-3 cells Gastric carcinoma Homo sapiens CVCL_1612
MKN-1 cells Gastric carcinoma Homo sapiens CVCL_1415
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
In Vivo Model
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.

    Click to Show/Hide
Response regulation We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model NUGC-3 cells Gastric carcinoma Homo sapiens CVCL_1612
MKN-1 cells Gastric carcinoma Homo sapiens CVCL_1415
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
In Vivo Model
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.

    Click to Show/Hide
Response regulation We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer (GC) cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy.
Nuclear receptor coactivator 4 (NCOA4)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Driver
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model NUGC-3 cells Gastric carcinoma Homo sapiens CVCL_1612
MKN-1 cells Gastric carcinoma Homo sapiens CVCL_1415
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
In Vivo Model
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.

    Click to Show/Hide
Response regulation We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy.
Ferritin heavy chain (FTH1)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model NUGC-3 cells Gastric carcinoma Homo sapiens CVCL_1612
MKN-1 cells Gastric carcinoma Homo sapiens CVCL_1415
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
In Vivo Model
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.

    Click to Show/Hide
Response regulation We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy.
References
Ref 1 Polyphyllin B Suppresses Gastric Tumor Growth by Modulating Iron Metabolism and Inducing Ferroptosis. Int J Biol Sci. 2023 Jan 31;19(4):1063-1079. doi: 10.7150/ijbs.80324. eCollection 2023.