DOI QR코드

DOI QR Code

Effect of Tetrodotoxin on the Proliferation and Gene Expression of Human SW620 Colorectal Cancer Cells

  • Bae, Yun-Ho (Department of Applied Animal Science, College of Animal Life Sciences, Kangwon National University) ;
  • Kim, Hun (Department of Applied Animal Science, College of Animal Life Sciences, Kangwon National University) ;
  • Lee, Sung-Jin (Department of Applied Animal Science, College of Animal Life Sciences, Kangwon National University)
  • Received : 2022.02.10
  • Accepted : 2022.03.29
  • Published : 2022.03.31

Abstract

Tetrodotoxin (TTX) is a natural neurotoxin found in several species of puffer fish belonging to Tetraodon fugu genus and has been reported to affect processes such as proliferation, metastasis and invasion of various cancer cells. However, it was not revealed which genes were influenced by these reactions. In this experiment, it was examined in human SW620 colorectal cancer cells. The proliferation of SW620 cells was significantly reduced when treated with 0, 1, 10 and 100 μM TTX for 48 h. It was confirmed using Annexin V-propidium iodide staining that some apoptosis was induced. Differentially expressed genes (DEGs) affecting cell proliferation through RNA sequencing (RNA-seq) were selected. The expression change of DEGs was confirmed by conducting quantitative real-time polymerase chain reaction (qRT-PCR). As a result, the mRNA expression of FOS and WDR48 genes was found to be increased in the 100 μM TTX treatment group compared to the control group. On the other hand, the mRNA expression of ALKBH7, NDUFA13, RIPPLY3 and SELENOM genes was found to be reduced, and in the case of the ALKBH7 gene was identified to show significant differences. This experiment suggests that TTX can be used as an important fundamental data to elucidate the mechanism that inhibits the proliferation of SW620 cells.

Keywords

Acknowledgement

This study was supported by National Research Foundation of Korea (Project number: 2017R1A2B2012125).

References

  1. Bouvard V, Loomis D, Guyton KZ, et al. Carcinogenicity of consumption of red and processed meat. Lancet Oncol. 2015. 16: 1599-1600. https://doi.org/10.1016/S1470-2045(15)00444-1
  2. Ceelen W, Pattyn P, Mareel M. Surgery, wound healing, and metastasis: Recent insights and clinical implications. Crit Rev Oncol Hematol. 2014. 89: 16-26. https://doi.org/10.1016/j.critrevonc.2013.07.008
  3. Cho YE, Lee S, Yoon K, et al. The antitumor mechanism and effects of tetrodotoxin: A literature review. J Acupunct Res. 2015. 32: 97-107.
  4. Corpet DE. Red meat and colon cancer: should we become vegetarians, or can we make meat safer?. Meat Sci. 2011. 89: 310-316. https://doi.org/10.1016/j.meatsci.2011.04.009
  5. Dariya B, Merchant N, Aliya S, Alam A, Nagaraju GP. EGFR and FGFR in growth and metastasis of colorectal cancer. Role of Tyrosine Kinases in Gastrointestinal Malignancies. 2018. pp. 141-170. Springer, Singapore.
  6. David C, Wendy A, Heinz-Josef L, et al. Colorectal cancer. Lancet Oncol. 2010. 375: 1030-1047. https://doi.org/10.1016/S0140-6736(10)60353-4
  7. Friedenreich CM, Neilson HK, Farris MS, Courneya KS. Physical activity and cancer outcomes: A precision medicine approach. Clin Cancer Res. 2016. 22: 4766-4775. https://doi.org/10.1158/1078-0432.ccr-16-0067
  8. Gianfredi V, Salvatori T, Villarini M, et al. Is dietary fibre truly protective against colon cancer? A systematic review and meta-analysis. Int J Food Sci Nutr. 2018. 69: 904-915. https://doi.org/10.1080/09637486.2018.1446917
  9. Gonzalez-Cano R, Ruiz-Cantero MC, Santos-Caballero M, et al. Tetrodotoxin, a potential drug for neuropathic and cancer pain relief?. Toxins (Basel). 2021. 13: 483. https://doi.org/10.3390/toxins13070483
  10. Hagen NA, du Souich P, Lapointe B, et al. Tetrodotoxin for moderate to severe cancer pain: A randomized, double blind, parallel design multicenter study. J Pain Symptom Manage. 2008. 35: 420-429. https://doi.org/10.1016/j.jpainsymman.2007.05.011
  11. Jeong SY. Surgical management of colorectal cancer. J Korean Am Med Assoc. 2010.
  12. Lee YS, Lee SH, Yang BK. Effects of bisphenol S on viability and reactive oxygen species of the sperm and ovarian granulosa cells in pigs. Ann Anim Resour Sci. 2018. 29: 166-171. https://doi.org/10.12718/AARS.2018.29.4.166
  13. Lyu YS, Park SK, Chung K, Chung JM. Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model. Brain Res. 2000. 871: 98-103. https://doi.org/10.1016/S0006-8993(00)02451-3
  14. Marcil J, Walczak JS, Guindon J, et al. Antinociceptive effects of tetrodotoxin (TTX) in rodents. Br J Anaesth. 2006. 96: 761-768. https://doi.org/10.1093/bja/ael096
  15. Na HK, Lee JY. Molecular basis of alcohol-related gastric and colon cancer. Int J Mol Sci. 2017. 18: 1116. https://doi.org/10.3390/ijms18061116
  16. Noguchi T, Ebesu JS. Puffer poisoning: Epidemiology and treatment. J Toxicol Toxin Rev. 2001. 20: 1-10. https://doi.org/10.1081/TXR-100103080
  17. Shannon J, White E, Shattuck AL, Potter JD. Relationship of food groups and water intake to colon cancer risk. Cancer Epidemiol Biomarkers Prev. 1996. 5: 495-502.
  18. Statistics Korea. Trends in cancer incidence and mortality. 2021. https://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=2770
  19. Xiao Z. Biosynthetic studies of tetrodotoxin and its anticancer activities assessment in vitro. MS thesis. Hong Kong Baptist University. 2014. Hong Kong, China.
  20. Yang Y, Luo Z, Hao Y, et al. mTOR-mediated Na+/Ca2+ exchange affects cell proliferation and metastasis of melanoma cells. Biomed Pharmacother. 2017. 92: 744-749. https://doi.org/10.1016/j.biopha.2017.05.104