Abstract
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.
Keywords:
Colorectal cancer, disulphide, oxidative stress, thiols
References
1Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA A Cancer J Clin. 2019;69:7e34.
2Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94:329e354.
3Cremers CM, Jakob U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem. 2013;288:26489e26496.
4Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. J Free Radic Biol Med. 2009;47:1329e1338.
5Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47:326e332.
6Biswas S, Chida AS, Rahman I. Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol. 2006;71:551e564.
7Vural 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.
8Hanikoglu 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.
9Korkmaz V, Kurdoglu Z, Alisik M, et al. Thiol/disulfide homeostasis in postmenopausal osteoporosis. J Endocrinol Investig. 2017;40:431e435.
10Demirseren 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.
11Ellman G, Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal Biochem. 1979;93:98e102.
12Chole 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.
13Patel 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.
14Dursun 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.
15Gonenc A, Ozkan Y, Torun M, Simsek B. Plasma malondialdehyde (MDA) levels in breast and lung cancer patients. J Clin Pharm Ther. 2001;26:141e144.
16Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991;51:794e798.
17Aykin-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.
18Vilema-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.
19Chang D, Wang F, Zhao YS, Pan HZ. Evaluation of oxidative stress in colorectal cancer patients. Biomed Environ Sci. 2008;21:286e289.
20Kang 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.
21Perse M. Oxidative stress in the pathogenesis of colorectal cancer: cause or consequence? BioMed Res Int. 2013;2013:725710.
22Kaplan M, Ates I, Yuksel M, et al. Thiol/disulphide homeostasis in celiac disease. World J Gastrointest Pharmacol Ther. 2017;8:120e126.
23Guney 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.
24Wu R, Feng J, Yang Y, et al. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS One. 2017;12. e0170003.
25Shen 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.
