Molecule Information

General Information of the Molecule (ID: Mol01180)

• Name: Glutathione S-transferase (GST) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: GST

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Ovarian cancer [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: GST colorimetric assay, RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Breast cancer [1]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: GST colorimetric assay, RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Liver cancer [1]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: GST colorimetric assay, RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Acute lymphocytic leukemia [2]

• Sensitive Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• In Vitro Model: CEM/ADR5000 cells; Bone marrow; Homo sapiens (Human); CVCL_D544
• Experiment for Molecule Alteration: Glutathione-S-transferase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.

Disease Class: Colorectal cancer [2]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• Experiment for Molecule Alteration: Glutathione-S-transferase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.

Disease Class: Cervical carcinoma [2]

• Sensitive Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Glutathione-S-transferase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.

Disease Class: Liver cancer [2]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Glutathione-S-transferase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.

References

• Ref 1: The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2020 Oct;77:153280. doi: 10.1016/j.phymed.2020.153280. Epub 2020 Jul 8.
• Ref 2: Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2019 Mar 1;55:269-281. doi: 10.1016/j.phymed.2018.06.046. Epub 2018 Jun 28.