2658-6649 2658-6657 Siberian Journal of Life Sciences and Agriculture Siberian Journal of Life Sciences and Agriculture Science and Innovation Center Publishing House 10.12731/2658-6649-2025-17-5-1248 IRRXEV https://discover-journal.ru/jour/index.php/sjlsa/article/view/1248 Биохимия, генетика и молекулярная биология Biochemistry, Genetics and Molecular Biology The effect of oxidative stress on epigenetic regulation of gene expression in intestinal cancer The effect of oxidative stress on epigenetic regulation of gene expression in intestinal cancer Jawad Widad Abed widad.jwad@qu.edu.iq 0000-0002-7305-4849 Siraj Noor Mahmood noor.a.ali.748209@gmail.com 0009-0002-1820-9307 Al-Qadisiyah University (Al-Qadisiya, Iraq) 30 11 2025 2025 17 5 229 241 18 10 2024 14 04 2025 16 03 2025 20252 W.A. Jawad, N.M. Siraj CC BY-NC-ND 4.0 https://discover-journal.ru/jour/index.php/sjlsa/article/view/1248

Background. Cancer is caused by the accumulation of genetic and epigenetic changes in the oncogenes and tumor-substituting genes. The discovery of the epigenetic pathways that control gene expression has substantially progressed in understanding cancer biology. Purpose. Investigation of epigenetic effects of oxidative stress on the regulation of gene expression in intestinal cancer. Methods. DLD-1 colorectal adenocarcinoma cells were treated with the oxidant 2,2’-Azobis (2-amidinopropane) dihydrochloride (AAPH) and the antioxidant hydroxytyrosol. Cellular viability, apoptosis, reactive oxygen species (ROS) production, and expression of key genes (CDH17, CXCL12, TGFB1) were examined. Results. Hydroxytyrosol treatment improved DLD-1 cell viability in a time-­dependent manner. AAPH-induced oxidative stress decreased cell viability and increased apoptosis and ROS production. Combination treatment with hydroxytyrosol and antioxidant enzymes enhanced these effects. Oxidative stress altered the expression of CDH17, CXCL12 and TGFB1, with TGFB1 showing a dose-dependent increase. Conclusion. Oxidative stress influences epigenetic regulation of gene expression in intestinal cancer cells. Combination therapies targeting both oxidative stress pathways and epigenetic mechanisms may be a promising approach for colorectal cancer treatment.

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(2018). The interplay between paraoxonase-1 and epigenetic changes in colorectal carcinoma. African Journal of Biochemistry Research, 12(7), 63–72. 7. Basak, D., Uddin, M. N., & Hancock, J. (2020). The role of oxidative stress and its counteractive utility in colorectal cancer (CRC). Cancers, 12(11), 3336–3369. https://doi.org/10.3390/cancers12113336. EDN: https://elibrary.ru/PHXKFE 8. Wijeratne, S. S. K., Cuppett, S. L., & Schlegel, V. (2005). Hydrogen peroxide induced oxidative stress damage and antioxidant enzyme response in Caco-2 human colon cells. Journal of Agricultural and Food Chemistry, 53(22), 8768–8774. https://doi.org/10.1021/jf0512003. EDN: https://elibrary.ru/XUBKTD 9. Wang, J., Luo, B., Li, X., Lu, W., Yang, J., Hu, Y., Huang, P., & Wen, S. (2017). Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells. Cell Death & Disease, 8(6), 2887–2896. 10. Cusimano, A., Balasus, D., Azzolina, A., Augello, G., Emma, M. R., Di Sano, C., Gramignoli, R., Strom, S. C., McCubrey, J. A., Montalto, G., & Cervello, M. (2017). Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation. International Journal of Oncology, 51(2), 533–544. 11. Zhang, R., Kang, K. A., Kim, K. C., Na, S.-Y., Chang, W. Y., Kim, G. Y., Kim, H. S., & Hyun, J. W. (2013). Oxidative stress causes epigenetic alteration of CDX1 expression in colorectal cancer cells. Gene, 524(2), 214–219. 12. Arita, A., & Costa, M. (2014). Oxidative stress and the epigenome in human disease. Journal of Genetics and Genome Research, 1(2), 1–5. 13. Sun, L., Luo, C., & Liu, J. (2014). Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation. Food & Function, 5(8), 1909–1914. 14. Robert, D. (2024). Introductory biostatistics for the health sciences. John Wiley & Sons: Awileg Medical Publication, 161–179. 15. Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019). Targeting epigenetic regulators for cancer therapy: Mechanisms and advances in clinical trials. Signal Transduction and Targeted Therapy, 4(1), 1–39. https://doi.org/10.1038/s41392-019-0095-0. EDN: https://elibrary.ru/HJWSXI 16. Gao, X., Zhang, Y., Burwinkel, B., Xuan, Y., Holleczek, B., Brenner, H., & Schöttker, B. (2019). The associations of DNA methylation alterations in oxidative stress-related genes with cancer incidence and mortality outcomes: A population-based cohort study. Clinical Epigenetics, 11(1), 1–9. https://doi.org/10.1186/s13148-018-0604-y. EDN: https://elibrary.ru/HMYSVB 17. Song, L., Liu, J., Jin, X., Li, Z., Zhao, M., & Liu, W. (2014). p,p′-Dichlorodiphenyldichloroethylene induces colorectal adenocarcinoma cell proliferation through oxidative stress. In C. Liu (Ed.), PLoS ONE, 9(11), 1–11. 18. Kim, S. J., Noh, T. H., Son, S., Kim, D. H., Kim, W., Lee, Y., Choo, J., Heo, G., Kim, M. J., Chung, H. Y., Jung, Y., Jung, J. H., Moon, H. R., & Im, E. (2018). Novel β-phenylacrylic acid derivatives exert anticancer activity by inducing Src-mediated apoptosis in wild-type KRAS colon cancer. Cell Death & Disease, 9(9), 1–17. https://doi.org/10.1038/s41419-018-0942-x. EDN: https://elibrary.ru/GULTLE