Evaluation of dynamic serum thiol-disulphide homeostasis in colorectal cancer
Received Date : 11 May 2019
Accepted Date : 03 Aug 2019
Doi: 10.1016/j.jons.2019.08.001 - Article's Language: EN
J Oncol Sci 5 (2019) 60e64
This is an open access article under the CC BY-NC-ND license
in recent years. Thiol and disulphide play an important role in cell signal mechanisms, antioxidant protection, and detoxification. In this study, we aimed to evaluate the role of Thiol-Disulphide homeostasis (TDH) in colorectal cancer (CRC) by using a new method. Material and Method: The patients (pts) who diagnosed with CRC and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. TDH tests were measured by the automated spectrophotometric method by describing Erel and Neselio glu. Thiol-disulphide homeostasis was also evaluated according to tumor stage and localization. Results: Eighty-eight pts with CRC and 110 control were enrolled. Native thiol (NT), disulphide and total thiol (TT) levels were significantly lower in patients compared with the control arm (Median NT: 402 e424, p ¼ 0.003; median Disulphide 18.7e21, p ¼ 0.011; median TT: 437e467, p ¼ 0.001). Thiol/disulphide balance was also maintained (p ¼ 0.149). TT and NT levels were not differed according to tumor localization whereas disulphide level was significantly higher in left-sided tumors than right-sided (19.9 e13.07 respectively, p ¼ 0.007). In addition, disulphide/NT ratio was also significantly higher in left-sided than right-sided (0.1e0.12 respectively, p ¼ 0.015). Thus, the balance of dynamic TDH is disrupted in favor of disulphide between left-sided and right-sided tumor. There was also no significant difference between thiol-disulphide levels and tumor stage whereas thiol level tends to lower in stage 4 disease (p ¼ 0.7). Conclusion: This is the first trial that evaluates the relationship with dynamic TDH and CRC according to tumor stage and localization. Thiol and disulphide may play an important role in the pathogenesis of CRC.
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA A Cancer J Clin. 2019;69:7e34. [Crossref]  [PubMed] 
  2. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94:329e354. [Crossref]  [PubMed]  [PMC] 
  3. Cremers CM, Jakob U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem. 2013;288:26489e26496. [Crossref]  [PubMed]  [PMC] 
  4. Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. J Free Radic Biol Med. 2009;47:1329e1338. [Crossref]  [PubMed]  [PMC] 
  5. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47:326e332. [Crossref]  [PubMed] 
  6. Biswas S, Chida AS, Rahman I. Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol. 2006;71:551e564. [Crossref]  [PubMed] 
  7. Vural G, Gumusyayla S, Bektas H, Deniz O, Alisik M, Erel O. Impairment of dynamic thiol-disulphide homeostasis in patients with idiopathic Parkinson's disease and its relationship with clinical stage of disease. Clin Neurol Neurosurg. 2017;153:50e55. [Crossref]  [PubMed] 
  8. Hanikoglu F, Hanikoglu A, Kucuksayan E, et al. Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer. Free Radic Res. 2016;50:S79eS84. [Crossref]  [PubMed] 
  9. Korkmaz V, Kurdoglu Z, Alisik M, et al. Thiol/disulfide homeostasis in postmenopausal osteoporosis. J Endocrinol Investig. 2017;40:431e435. [Crossref]  [PubMed] 
  10. Demirseren DD, Cicek C, Alisik M, Demirseren ME, Aktas A, Erel O. Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma. Cutan Ocul Toxicol. 2017;36:278e282. [Crossref]  [PubMed] 
  11. Ellman G, Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal Biochem. 1979;93:98e102. [Crossref] 
  12. Chole RH, Patil RN, Basak A, Palandurkar K, Bhowate R. Estimation of serum malondialdehyde in oral cancer and precancer and its association with healthy individuals, gender, alcohol, and tobacco abuse. J Cancer Res Ther. 2010;6: 487e491. [Crossref]  [PubMed] 
  13. Patel BP, Rawal UM, Dave TK, et al. Lipid peroxidation, total antioxidant status, and total thiol levels predict overall survival in patients with oral squamous cell carcinoma. Integr Cancer Ther. 2007;6:365e372. [Crossref]  [PubMed] 
  14. Dursun H, Bilici M, Uyanik A, Okcu N, Akyuz M. Antioxidant enzyme activities and lipid peroxidation levels in erythrocytes of patients with oesophageal and gastric cancer. J Int Med Res. 2006;34:193e199. [Crossref]  [PubMed] 
  15. Gonenc A, Ozkan Y, Torun M, Simsek B. Plasma malondialdehyde (MDA) levels in breast and lung cancer patients. J Clin Pharm Ther. 2001;26:141e144. [Crossref]  [PubMed] 
  16. Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991;51:794e798.
  17. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J. 2009;418:29e37. [Crossref]  [PubMed]  [PMC] 
  18. Vilema-Enriquez G, Arroyo A, Grijalva M, Amador-Zafra RI, Camacho J. Molecular and cellular effects of hydrogen peroxide on human lung cancer cells: potential therapeutic implications. Oxid Med Cell Longev. 2016;2016:1908164. [Crossref]  [PubMed]  [PMC] 
  19. Chang D, Wang F, Zhao YS, Pan HZ. Evaluation of oxidative stress in colorectal cancer patients. Biomed Environ Sci. 2008;21:286e289. [Crossref] 
  20. Kang KA, Kim KC, Bae SC, Hyun JW. Oxidative stress induces proliferation of colorectal cancer cells by inhibiting RUNX3 and activating the Akt signaling pathway. Int J Oncol. 2013;43:1511e1516. [Crossref]  [PubMed] 
  21. Perse M. Oxidative stress in the pathogenesis of colorectal cancer: cause or consequence? BioMed Res Int. 2013;2013:725710. [Crossref]  [PubMed]  [PMC] 
  22. Kaplan M, Ates I, Yuksel M, et al. Thiol/disulphide homeostasis in celiac disease. World J Gastrointest Pharmacol Ther. 2017;8:120e126. [Crossref]  [PubMed]  [PMC] 
  23. Guney T, Kanat ILF, Alkan A, et al. Assessment of serum thiol/disulfide homeostasis in multiple myeloma patients by a new method. Redox Rep. 2016: 1e6. [Crossref]  [PubMed] 
  24. Wu R, Feng J, Yang Y, et al. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS One. 2017;12. e0170003. [Crossref]  [PubMed]  [PMC] 
  25. Shen H, Yang J, Huang Q, et al. Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol. 2015;21:6470e6478. [Crossref]  [PubMed]  [PMC]