Investigation of the Antitumoral Activity of Syringic Acid on HT-29 Cells: An In Vitro Study

Abstract

Abstract Colorectal cancer (CRC) is one of the most common cancers in the world with high mortality rates, and it is the second leading cause of cancer-related deaths worldwide and it is estimated that more than 930,000 deaths will occur due to CRC. In addition to genetic and environmental factors, oxidative stress, lipid peroxidation and parameter changes in the antioxidant system are among the risk factors. Syringic acid (SA) which contains polyphenolic compounds, has antioxidant, anti-lipid peroxidative and anti-cancer effects. Due to these effects, syringic acid may have a healing effect on HT-29 cells. In our study, we determined the effect of SA on cell viability on HT-29 cells with MTT, and its effects on antioxidant and oxidant parameters with TAC-TOS tests. Syringic acid decreased viability, increased TAC levels and did not cause a significant change in TOS levels in HT-29 cells. These findings may indicate that SA has curative effects on CRC. However, more studies are needed for clinical uses.

Keywords

• Anticancer
• Antioxidant
• Colorectal cancer
• HT-29 Cells
• Syringic acid

References

1. Abaza, M.-S., Al-Attiyah, R. a., Bhardwaj, R., Abbadi, G., Koyippally, M., & Afzal, M. (2013). Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells. Pharmaceutical Biology, 51(9), 1110-1124. https://doi.org/10.3109/13880209.2013.781194
2. Ahmed, M. (2020). Colon Cancer: A Clinician's Perspective in 2019. Gastroenterology Res, 13(1), 1-10. https://doi.org/10.14740/gr1239
3. Cikman, O., Soylemez, O., Ozkan, O. F., Kiraz, H. A., Sayar, I., Ademoglu, S., Taysi, S., & Karaayvaz, M. (2015). Antioxidant Activity of Syringic Acid Prevents Oxidative Stress in l-arginine-Induced Acute Pancreatitis: An Experimental Study on Rats. Int Surg, 100(5), 891-896. https://doi.org/10.9738/intsurg-d-14-00170.1
4. Clemente, S. M., Martínez-Costa, O. H., Monsalve, M., & Samhan-Arias, A. K. (2020). Targeting Lipid Peroxidation for Cancer Treatment. Molecules, 25(21), 5144. https://www.mdpi.com/1420-3049/25/21/5144
5. Ferah Okkay, I., Okkay, U., Gundogdu, O. L., Bayram, C., Mendil, A. S., Ertugrul, M. S., & Hacimuftuoglu, A. (2022). Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence. Neuroscience Letters, 769, 136385. https://doi.org/https://doi.org/10.1016/j.neulet.2021.136385
6. Gheena, S., & Ezhilarasan, D. (2019). Syringic acid triggers reactive oxygen species–mediated cytotoxicity in HepG2 cells. Human & Experimental Toxicology, 38(6), 694-702. https://doi.org/10.1177/0960327119839173
7. Johdi, N. A., & Sukor, N. F. (2020). Colorectal Cancer Immunotherapy: Options and Strategies. Front Immunol, 11, 1624. https://doi.org/10.3389/fimmu.2020.01624
8. Kuipers, E. J., Grady, W. M., Lieberman, D., Seufferlein, T., Sung, J. J., Boelens, P. G., van de Velde, C. J., & Watanabe, T. (2015). Colorectal cancer. Nat Rev Dis Primers, 1, 15065. https://doi.org/10.1038/nrdp.2015.65

9. Li, J., Ma, X., Chakravarti, D., Shalapour, S., & DePinho, R. A. (2021). Genetic and biological hallmarks of colorectal cancer. Genes Dev, 35(11-12), 787-820. https://doi.org/10.1101/gad.348226.120
10. Lin, S., Li, Y., Zamyatnin, A. A., Jr., Werner, J., & Bazhin, A. V. (2018). Reactive oxygen species and colorectal cancer. J Cell Physiol, 233(7), 5119-5132. https://doi.org/10.1002/jcp.26356
11. Long, A. G., Lundsmith, E. T., & Hamilton, K. E. (2017). Inflammation and Colorectal Cancer. Current Colorectal Cancer Reports, 13(4), 341-351. https://doi.org/10.1007/s11888-017-0373-6
12. Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., & Rodriguez Yoldi, M. J. (2017). Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci, 18(1). https://doi.org/10.3390/ijms18010197
13. Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., & Rodriguez Yoldi, M. J. (2017). Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. International Journal of Molecular Sciences, 18(1), 197. https://www.mdpi.com/1422-0067/18/1/197
14. Mihanfar, A., Darband, S. G., Sadighparvar, S., Kaviani, M., Mirza-Aghazadeh-Attari, M., Yousefi, B., & Majidinia, M. (2021). In vitro and in vivo anticancer effects of syringic acid on colorectal cancer: Possible mechanistic view. Chemico-Biological Interactions, 337, 109337. https://doi.org/https://doi.org/10.1016/j.cbi.2020.109337
15. Okkay, U., & Ferah Okkay, I. (2022). In vitro neuroprotective effects of allicin on Alzheimer’s disease model of neuroblastoma cell line. Journal of Surgery and Medicine, 6(2), 209-212. https://doi.org/10.28982/josam.1068336
16. Pacal, I., Karaboga, D., Basturk, A., Akay, B., & Nalbantoglu, U. (2020). A comprehensive review of deep learning in colon cancer. Computers in Biology and Medicine, 126, 104003. https://doi.org/https://doi.org/10.1016/j.compbiomed.2020.104003
17. Pei, J., Velu, P., Zareian, M., Feng, Z., & Vijayalakshmi, A. (2021). Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells. Front Nutr, 8, 788929. https://doi.org/10.3389/fnut.2021.788929
18. Pei, J., Velu, P., Zareian, M., Feng, Z., & Vijayalakshmi, A. (2021). Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells [Original Research]. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.788929
19. Sancak, E. B., Akbas, A., Silan, C., Cakir, D. U., Turkon, H., & Ozkanli, S. S. (2016). Protective effect of syringic acid on kidney ischemia-reperfusion injury. Renal Failure, 38(4), 629-635. https://doi.org/10.3109/0886022X.2016.1149868
20. Schmitt, M., & Greten, F. R. (2021). The inflammatory pathogenesis of colorectal cancer. Nat Rev Immunol, 21(10), 653-667. https://doi.org/10.1038/s41577-021-00534-x
21. Sezen, S., Ertuğrul, M. S., Balpınar, Ö., Bayram, C., Özkaraca, M., Okkay, I. F., Hacımüftüoğlu, A., & Güllüce, M. (2023). Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-023-30417-8
22. Simon, K. (2016). Colorectal cancer development and advances in screening. Clin Interv Aging, 11, 967-976. https://doi.org/10.2147/cia.S109285
23. Smith, K. M., & Desai, J. (2018). Nivolumab for the treatment of colorectal cancer. Expert Rev Anticancer Ther, 18(7), 611-618. https://doi.org/10.1080/14737140.2018.1480942
24. Srinivasulu, C., Ramgopal, M., Ramanjaneyulu, G., Anuradha, C. M., & Suresh Kumar, C. (2018). Syringic acid (SA) ‒ A Review of Its Occurrence, Biosynthesis, Pharmacological and Industrial Importance. Biomedicine & Pharmacotherapy, 108, 547-557. https://doi.org/https://doi.org/10.1016/j.biopha.2018.09.069
25. Thanikachalam, K., & Khan, G. (2019). Colorectal Cancer and Nutrition. Nutrients, 11(1), 164. https://www.mdpi.com/2072-6643/11/1/164
26. WHO. (2023). Colorectal cancer. Retrieved 02.10 from https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer#:~:text=Colorectal%20cancer%20is%20the%20third,people%20aged%2050%20and%20above.
27. Yücel, A. F., Kemik, O., Kemik, A. S., Purisa, S., & Tüzün, I. S. (2012). Relationship between the levels of oxidative stress in mesenteric and peripheral serum and clinicopathological variables in colorectal cancer. Balkan Med J, 29(2), 144-147. https://doi.org/10.5152/balkanmedj.2011.035