Prognostic Significance of Altered Blood and Tissue Glutathione Levels in Head and Neck Squamous Cell Carcinoma Cases

  • Khan, Sami Ullah (Department of Biosciences, COMSATS Institute of Information and Technology) ;
  • Mahjabeen, Ishrat (Department of Biosciences, COMSATS Institute of Information and Technology) ;
  • Malik, Faraz Arshad (Department of Biosciences, COMSATS Institute of Information and Technology) ;
  • Kayani, Mahmood Akhtar (Department of Biosciences, COMSATS Institute of Information and Technology)
  • 발행 : 2014.10.11


Glutathione is a thiol compound that plays an important role in the antioxidant defense system of the cell and its deficiency leads to an increased susceptibility to oxidative stress and, thus, progression of many disease states including head and neck cancer. In the present study, alterations of glutathione levels were investigated in study cohort of 500 samples (cohort 1 containing 200 head and neck cancer blood samples along with 200 healthy controls and cohort II with 50 head and neck squamous cell carcinoma tissue samples along with 50 control tissues) by high performance liquid chromatography. The results indicated that mean blood glutathione levels were significantly reduced in head and neck cancer patients (p<0.001) compared to respective controls. In contrast, the levels of glutathione total (p<0.05) and glutathione reduced (p<0.05) were significantly elevated in head and neck squamous cell carcinoma tissues compared to the adjacent cancer-free control tissues. In addition to this, pearson correlation performed to correlate different tissue glutathione levels (GSH) with clinical/pathological parameters demonstrated a significant negative correlation between pT-stage and GSH level ($r=-0.263^{**}$; p<0.01), C-stage and GSH level ($r=-0.335^{**}$; p<0.01), grade and GSH ($r=-0.329^{**}$; p<0.01) and grade versus redox index ($r=-0.213^{**}$; p<0.01) in HNSCC tissues. Our study suggests that dysregulation of glutathione levels in head and neck cancer has the potential to predict metastasis, and may serve as a prognostic marker.


  1. Balendiran GK, Dabur R, Fraser D (2004). The role of glutathione in cancer. Cell Biochem Funct, 22, 343-52.
  2. Bray F, Ren JS, Masuyer E, et al (2012). Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer, 132, 1133-45.
  3. Burlakova EB, Zhizhina GP, Gurevich SM, et al (2010). Biomarkers of oxidative stress and smoking in cancer patients. J Can Res Ther, 6, 47-53.
  4. Cacciatore I, Cornacchia C, Pinnen F, Mollica A, Di Stefano A (2010). Prodrug approach for increasing cellular glutathione levels. Molecules, 15, 1242-64.
  5. Lu C, Margaret RS, Hua Z, et al (2006). Association between Glutathione-S-transferase II polymorphism and survival in patients with advanced non small cell lung carcinoma (NSCLC). Cancer, 106, 441-7.
  6. Erden-Inal M, Sunal E, Kanbak G (2002). Age-related changes in the glutathione redox system. Cell Biochem Funct, 20, 61-6.
  7. Gherghel D, Griffiths HR, Hilton EJ, Cunliffe IA, Hosking SL (2005). Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci, 46, 877-83.
  8. Gherghel D, Mroczkowska S, Qin L (2013). Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma. Glaucoma, 54, 3333-9.
  9. Gupta A, Bhatt MLB, Misra MK (2010). Assessment of free radical-mediated damage in head and neck squamous cell carcinoma patients and after treatment with radiotherapy. Indian J Biochem Biophys, 47, 96-9.
  10. Komatsu D, Kato M, Nakayama J, et al (2008). NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression. Oncogene, 27, 4724-32.
  11. Kruk J, Duchnik E (2014). Oxidative stress and skin diseases:possible role of physical activity. Asian Pac J Cancer Prev, 15, 561-8.
  12. Loyha K, Vatanasapt P, Promthet S, Parkin DM (2012). Risk factors for oral cancer in northeast Thailand. Asian Pac J Cancer Prev, 13, 5087-90.
  13. Mahjabeen I, Baig RM, Masood N, et al (2011). OGG1 Gene sequence variation in head and neck cancer patients in Pakistan. Asian Pacific J Cancer Prev, 12, 2779-83.
  14. Manoharan S, Singh AK, Suresh K, et al (2012). Antitumor initiating potential of andrographolide in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Asian Pac J Cancer Prev, 13, 5701-8.
  15. Masood N, Yasmin A, Kayani MA (2013). Genetic deletions of GSTM1 and GSTT1 in head and neck cancer: review of the literature from 2000 to 2012. Asian Pac J Prev, 14, 3535-9.
  16. Muchova J, Garaiova I, Sustrova M, et al (2007). The redox state of glutathione in erytjrocytes of individuals in down syndrome. Bratisl Lek Listry, 108, 70-4.
  17. Narasimhan R, Vaithiyanathan M, Janardanam V (2011). Neuroprotective effect of sesamol in glioma induced in rats. Bio Med Int, 2, 22-7.
  18. Nagamma, Anjaneyulu, Baxi, Dayaram P, Singh P (2011). Cigarette smoking and lipid peroxidation and antioxidant status in cancer patients from western Nepal. Asian Pac J Cancer Prev, 12, 313-6.
  19. Nisha, Sachdeva A, Lal H (2008). Some oxidative stress related parameters in patients with head and neck carcinoma. Indian J Clin Biochem, 23, 38-40.
  20. Oyagbemi AA, OI Azeez, AB Saba (2009). Interactions between reactive oxygen species and cancer: the roles of natural dietary antioxidants and their molecular mechanisms of action. Asian Pac J Cancer Prev, 10, 535-44.
  21. Pruegsanusak K, Peeravut S, Leelamanit V, et al (2012). Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand. Asian Pac J Cancer Prev, 13, 885-90.
  22. Rasheed MH, Beevi SS, Geetha A (2007). Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma. Oral Oncology, 43, 333-8.
  23. Richie JP, Kleinman W, Marina P, Muscat JE (2008). Blood iron, glutathione, and micronutrient levels and the risk of oral cancer. Nutr Cancer, 60, 474-82.
  24. Schafer FQ, Buettner GR (2001). Redox environment of cell as viewed through the redox state of the glutathione disulphide/glutathione couple. Free Radic Biol Med, 30, 1191-212.
  25. Shetty SR, Babu S, Kumari S, et al (2013). Serum glutathione levels in oral leukoplakia and oral squamous cell carcinoma-a clinicopathological study. Am J Cancer Prev, 1, 1-3.
  26. Singh, YP, Sachdeva OP, Aggarwal SK, Chugh K, Harbans L (2008). Blood glutathione levels in head and neck malignances. Indian J Clinc Biochem, 23, 290-2.
  27. Taya S, Punvittayagul C, Inboot W, Fukushima S, Wongpoomchai R (2014). Cleistocalyx nervosum extract ameliorates chemical-induced oxidative stress in early stages of rat hepatocarcinogenesis. Asian Pac J Cancer Prev, 15, 2825-30.
  28. Trachootham D, Alexandre J, Huang P (2009). Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov, 7, 579-91.
  29. Valluru L, Dasari S, Wudayagiri R. (2014). Role of free radicals and antioxidants in gynecological cancers: current status and future prospects. Oxid Antioxid Med Sci, 13, 15-26.
  30. Wahid M, Mahjabeen I, Baig RM, Kayani MA (2013). Expression of CYP1A1 and GSTP1 in human brain tumor tissues in Pakistan. Asian Pac J Cancer Prev, 14, 7187-91.
  31. Waly MI, Ali A, Guizani N, et al (2012). Pomegranate (Punica granatum) peel extract efficacy as a dietary antioxidant against azoxymethane-induced colon cancer in rat. Asian Pac J Cancer Prev, 13, 4051-5.
  32. Yao L, Ji G, Gu A, Zhao P, Liu N (2012). An updated pooled analysis of glutathione s-transferase genotype polymorphisms and risk of adult gliomas. Asian Pac J Cancer Prev, 13, 157-63.
  33. Yeh CC, Hou MF, Wu SH et al (2006). A study of glutathione status in the blood and tissues of patients with breast cancer. Cell Biochem Funct, 24, 555-9.