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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Expression of CYP1A1 and GSTP1 in human brain tumor tissues in Pakistan
Mussarat Wahid1, Ishrat Mahjabeen, Ruqia Mehmood Baig
1Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan
Abstract:
Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.
Insights
Altered expression of xenobiotic metabolizing genes, specifically increased CYP1A1 and decreased glutathione-S-transferases (GSTs), is linked to brain tumor development. This finding may aid in predicting cancer risk and prevention strategies.
Area of Science:
- Biochemistry and Molecular Biology
- Oncology
- Genetics
Background:
- Xenobiotic metabolizing enzymes, including cytochrome P450 (CYP) and glutathione-S-transferases (GSTs), play crucial roles in detoxifying or activating chemical compounds.
- Deregulation of these enzymes can lead to the formation of DNA adducts, potentially contributing to cancer development.
- The specific role of xenobiotic metabolizing gene expression in brain tumorigenesis requires further investigation.
Purpose of the Study:
- To investigate the association between the deregulation of metabolizing genes and brain tumorigenesis.
- To analyze the expression profiles of CYP1A1 and GSTP1 in brain tumor patients and controls.
Main Methods:
- Western blotting was used to study the expression of CYP1A1 and GSTP1 in a cohort of 36 brain tumor patients and controls.
- Enzyme-linked immunosorbent assay (ELISA) was employed to analyze protein expression of GSTs in the same cohort.
- Statistical analyses, including fold change and odds ratios, were used to determine significance.
Main Results:
- CYP1A1 expression was significantly elevated in brain tumor tissues compared to normal tissues (~4 fold increase).
- GSTP1 expression was significantly reduced in brain tumor tissues, with greater downregulation in higher-grade lesions.
- Overall GSTs levels were significantly downregulated in brain tumor patients, particularly in advanced tumor grades (III-IV).
Conclusions:
- Altered expression of xenobiotic metabolizing genes, including increased CYP1A1 and decreased GSTs, may be implicated in brain tumor development.
- These findings suggest that investigating the expression of these genes could offer insights into individual cancer risk prediction.
- Further research into these genetic alterations may contribute to the development of cancer prevention strategies.
