- Volume 14 Issue 12
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Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan
- Wahid, Mussarat (Department of Biosciences, COMSATS Institute of Information and Technology) ;
- Mahjabeen, Ishrat (Department of Biosciences, COMSATS Institute of Information and Technology) ;
- Baig, Ruqia Mehmood (Department of Biosciences, COMSATS Institute of Information and Technology) ;
- Kayani, Mahmood Akhtar (Department of Biosciences, COMSATS Institute of Information and Technology)
- Published : 2013.12.31
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.
- Androutsopoulos VP, Tsatsakis AM, Spandidos DA (2009). Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer, 9, 187. https://doi.org/10.1186/1471-2407-9-187
- Briqelius-Flohe R, Kipp A (2009). Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta, 1790, 1555-68. https://doi.org/10.1016/j.bbagen.2009.03.006
- Chang Jiang X, Christina Yong T, Li Tao K (2005). Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics. Arch Pharm Res, 28, 249-68. https://doi.org/10.1007/BF02977789
- Chang TJ, Chang H, Chen P, et al (2007). Requirement of aryl hydrocarbon receptor overexpression for CYP1B1 upregulation and cell growth in human lung adenocarcinomas. Clin Cancer Res, 13, 38-5. https://doi.org/10.1158/1078-0432.CCR-06-1166
- Conway DE, Williams MR, Eskin SG, et al (2010). Endothelial cell responses to atheroprone flow are driven by two separate flow components: low time-average shear stress and fluid flow reversal. Am J Physiol Heart Circ Physiol, 298, 367-74. https://doi.org/10.1152/ajpheart.00565.2009
- Curran JE, Weinstein SR, Griffiths LR (2000). Polymorphisms of glutathione S transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett, 153, 113-20. https://doi.org/10.1016/S0304-3835(00)00361-X
- Davis F G, McCarthy B J (2001). Current epidemiological trends and surveillance issues in brain tumors. Expert Rev Anticancer Ther, 1, 395-1,401. https://doi.org/10.1586/14737188.8.131.525
- Dutheil F, Dauchy S, Diry M, et al (2009). Xenobiotic-Metabolizing Enzymes and Transporters in the Normal Human Brain: Regional and Cellular Mapping as a Basis for Putative Roles in Cerebral Functio, drug metabolismand disposition, 7, 37.
Eralp Y, Keskin S, Akisik E, et al (2013). Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase
$2\alpha$expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Am J Clin Oncol, 36, 215-23. https://doi.org/10.1097/COC.0b013e318243913f
- Hafeez S, Ahmed A, Rashid AZ, et al (2012). Downregulation of CYP1A1 expression in Breast Cancer. APJCP, 13, 1757-60.
- Jancova P, Anzenbacher P, Anzenbacher E (2010). Phase II Drug Metabolizing Enzyme. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 154, 103-16. https://doi.org/10.5507/bp.2010.017
- Joan AN, Adjanie AK P, Diana EM D (2010). Structure and function of the blood brain barrier. Neurobiol Dis, 37, 13- 25. https://doi.org/10.1016/j.nbd.2009.07.030
- Kasai S, Ishigaki T, Takumi R, et al (2013). Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells. Biochim Biophys Acta. 1830, 2509-16. https://doi.org/10.1016/j.bbagen.2012.11.007
- Koh W, Nelson H.H, Yuan J et al (2011). Glutathione S-transferase (GST) gene polymorphisms, cigarette smoking and colorectal cancer risk among Chinese in Singapore. Carcinogenesis, 32, 1507-11. https://doi.org/10.1093/carcin/bgr175
- Liu X, Tu M, Kelly RS et al (2004). Development of a computational approach to predict blood brain barrier permeability. Drug Metab Dispos, 32, 132-9. https://doi.org/10.1124/dmd.32.1.132
- Masood N, Kayani MA (2011). Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients. Genet Mol Biol, 34 , 533-8. https://doi.org/10.1590/S1415-47572011005000034
- Milne E, Greenop KR, Scott RJ, et al (2013). Parental smoking and risk of childhood brain tumors. Int J Cancer, 133, 253-9. https://doi.org/10.1002/ijc.28004
- Narasimhan R, Vaithiyanathan M, Janardanam V (2011). Neuroprotective effect of sesamol in glioma induced in rats. Bio Med Int, 2, 22-7.
- Nosheen M, Ishrat M, Malik FA, et al (2010). Association of GSTM1 and GSTT1 gene deletions with risk of head and neck cancer in Pakistani - a case control study: Asian Pac J Cancer Prev, 11, 1-6.
- Nosheen M, Malik FA, KIyani FA et al (2010). Unusual intronic variant in GSTP1 in head and neck cancer in Pakistan. Asian Pac J Cancer Prev, 13, 1683-6. https://doi.org/10.7314/APJCP.2012.13.4.1683
- Nosheen M, Malik FA, Kiyani MA (2011). Expression of xenobiotic metabolizing genes in head and neck cancer tissues. Asian Pac J Cancer Prev, 12, 377-82.
- Okino ST, Pookot D, Majid S, et al (2007). Chromatin changes on the GSTP1 promoter associated with its inactivation in prostate cancer. Mol Carcinog, 46, 839-49. https://doi.org/10.1002/mc.20313
- Peters S, Glass DC, Reid A, et al (2013). Parental occupational exposure to engine exhausts and childhood brain tumors. Int J Cancer, 132, 2975-9. https://doi.org/10.1002/ijc.27972
- Ravindranath V, Bhamrea S, Bhagwat SV, et al (1995). Xenobiotic metabolism in brain. Toxicol Lett, 82/83, 633-8. https://doi.org/10.1016/0378-4274(95)03508-7
Re A, Aiello A, Nani S, et al (2011). Silencing of GSTP1, a Prostate Cancer Prognostic Gene, by the Estrogen Receptor-
$\beta$and Endothelial Nitric Oxide Synthase Complex. Mol Endocrinol, 25, 2003-16. https://doi.org/10.1210/me.2011-1024
- Ritchie KJ, Walsh S, Sansom OJ, et al (2009). Markedly enhanced colon tumorigenesis in Apc(Min) mice lacking glutathione S-transferase Pi. Proc Natl Acad Sci USA, 106, 20859-64. https://doi.org/10.1073/pnas.0911351106
- Salnikova LE, Zelinskaya NI, Belopolskaya OB, et al (2013). Association study of xenobiotic detoxication and repair genes with malignant brain tumors in children. Acta Naturae, 2, 58-65
- Schwartzbaum JA, Ahlbom A, Lonn S, et al (2007). An International Case-Control Study of Glutathione Transferase and Functionally Related Polymorphisms and Risk of Primary Adult Brain Tumors. Cancer Epidemiol Biomarkers Prev, 16, 559-65. https://doi.org/10.1158/1055-9965.EPI-06-0918
- Shah PP, Saurabh K, Pant MC, et al (2009). Evidence for increased cytochrome P450 1A1 expression in blood lymphocytes of lung cancer patients. Mutat Res, 670, 74-8. https://doi.org/10.1016/j.mrfmmm.2009.07.006
- Shen K, Ji L, Chen Y, et al (2011). Influence of glutathione levels and activity of glutathione-related enzymes in the brains of tumor-bearing mice. BioSci Trends, 5, 30-7. https://doi.org/10.5582/bst.2011.v5.1.30
- Shukla RK, Tilak AR, Kumar C, et al (2013). Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population. Asian Pac J Cancer Prev, 14, 3345-9. https://doi.org/10.7314/APJCP.2013.14.5.3345
- Thomas E, Manfred V (2005). Glutathione-related Enzymes Contribute to Resistance of Tumor Cells and Low Toxicity in Normal Organs to Artesunate. In vivo 19, 225-32.
- Tsutomu S (2006). Xenobiotic-Metabolizing Enzymes Involved in Activation and Detoxification of Carcinogenic Polycyclic Aromatic Hydrocarbons. Drug Metabolism Pharmacokinet, 21, 257-76. https://doi.org/10.2133/dmpk.21.257
- Uchida Y, Chiyomaru T, Enokida H, et al (2013). MiR-133a induces apoptosis through direct regulation of GSTP1 in bladder cancer cell lines. Urol Oncol, 31, 115-23. https://doi.org/10.1016/j.urolonc.2010.09.017
- Wincent E, Bengtsson J, Bardbori AM, et al (2012). Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor. Proc Natl Acad Sci USA, 109, 4479-84 https://doi.org/10.1073/pnas.1118467109
- Yao L, Ji G, Gu A, et al (2012). An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas. Asian Pac J Cancer Prev, 13, 157-63. https://doi.org/10.7314/APJCP.2012.13.1.157
- Prognostic Significance of Altered Blood and Tissue Glutathione Levels in Head and Neck Squamous Cell Carcinoma Cases vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7603
- Lack of Association Between CYP1A1 Polymorphisms and Risk of Bladder Cancer: a Meta-analysis vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.4071
- Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors vol.10, pp.11, 2015, https://doi.org/10.1371/journal.pone.0143285
- Association Between GSTP1 Ile105Val Genetic Polymorphism and Dependency to Heroin and Opium pp.1573-4927, 2018, https://doi.org/10.1007/s10528-018-9885-2