DOI QR코드

DOI QR Code

Antimetastatic effect of fucoidan against non-small cell lung cancer by suppressing non-receptor tyrosine kinase and extracellular signal-related kinase pathway

  • Nareenath Muneerungsee (Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University) ;
  • Supita Tanasawet (Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University) ;
  • Wanida Sukketsiri (Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University)
  • Received : 2023.03.23
  • Accepted : 2023.06.15
  • Published : 2023.10.01

Abstract

BACKGROUND/OBJECTIVES: Fucoidan, a polysaccharide content in brown algae, has been reported to inhibit the growth of cancer cells. The present study aimed to investigate the suppression effects of fucoidan on A549 non-small cell lung cancer cells migration. MATERIALS/METHODS: The anti-migratory activity of fucoidan in A549 cells was examined by wound healing assay and phalloidin-rhodamine staining in response to fucoidan (0-100 ㎍/mL) treatment for 48 h. Western blot analysis was performed to clarify the protein expressions relevant to migratory activity. RESULTS: Fucoidan (25-100 ㎍/mL) significantly suppressed A549 cells migration together with reduced the intensity of phalloidin-rhodamine which detect filopodia and lamellipodia protrusions at 48 h of treatment. The protein expression indicated that fucoidan significantly suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK). In addition, the phosphorylation of p38 in A549 cells was found to be increased. CONCLUSIONS: Our data conclude that fucoidan exhibits anti-migratory activities against lung cancer A549 cells mediated by inhibiting ERK1/2 and FAK-Src pathway.

Keywords

Acknowledgement

We would like to acknowledge Faculty of Science, Prince of Songkhla University, Thailand, providing the experimental supports. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

References

  1. Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung cancer. Ann Glob Health 2019;85:8.
  2. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018;553:446-54. https://doi.org/10.1038/nature25183
  3. Olson MF, Sahai E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis 2009;26:273-87. https://doi.org/10.1007/s10585-008-9174-2
  4. Svitkina T. The actin cytoskeleton and actin-based motility. Cold Spring Harb Perspect Biol 2018;10:a018267.
  5. Carelli S, Zadra G, Vaira V, Falleni M, Bottiglieri L, Nosotti M, Di Giulio AM, Gorio A, Bosari S. Up-regulation of focal adhesion kinase in non-small cell lung cancer. Lung Cancer 2006;53:263-71. https://doi.org/10.1016/j.lungcan.2006.06.001
  6. Chikara S, Lindsey K, Borowicz P, Christofidou-Solomidou M, Reindl KM. Enterolactone alters FAK-Src signaling and suppresses migration and invasion of lung cancer cell lines. BMC Complement Altern Med 2017;17:30.
  7. Masraksa W, Tanasawet S, Hutamekalin P, Wongtawatchai T, Sukketsiri W. Luteolin attenuates migration and invasion of lung cancer cells via suppressing focal adhesion kinase and non-receptor tyrosine kinase signaling pathway. Nutr Res Pract 2020;14:127-33. https://doi.org/10.4162/nrp.2020.14.2.127
  8. Mitra SK, Schlaepfer DD. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 2006;18:516-23. https://doi.org/10.1016/j.ceb.2006.08.011
  9. van Weelden G, Bobinski M, Okla K, van Weelden WJ, Romano A, Pijnenborg JM. Fucoidan structure and activity in relation to anti-cancer mechanisms. Mar Drugs 2019;17:32.
  10. Kim H, Ahn JH, Song M, Kim DW, Lee TK, Lee JC, Kim YM, Kim JD, Cho JH, Hwang IK, et al. Pretreated fucoidan confers neuroprotection against transient global cerebral ischemic injury in the gerbil hippocampal CA1 area via reducing of glial cell activation and oxidative stress. Biomed Pharmacother 2019;109:1718-27. https://doi.org/10.1016/j.biopha.2018.11.015
  11. Wang Y, Wang Q, Han X, Ma Y, Zhang Z, Zhao L, Guan F, Ma S. Fucoidan: a promising agent for brain injury and neurodegenerative disease intervention. Food Funct 2021;12:3820-30. https://doi.org/10.1039/D0FO03153D
  12. Narayani SS, Saravanan S, Ravindran J, Ramasamy MS, Chitra J. In vitro anticancer activity of fucoidan extracted from Sargassum cinereum against Caco-2 cells. Int J Biol Macromol 2019;138:618-28. https://doi.org/10.1016/j.ijbiomac.2019.07.127
  13. Atashrazm F, Lowenthal RM, Woods GM, Holloway AF, Dickinson JL. Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs 2015;13:2327-46. https://doi.org/10.3390/md13042327
  14. Woonnoi W, Chotphruethipong L, Tanasawet S, Benjakul S, Sutthiwong N, Sukketsiri W. Hydrolyzed collagen from salmon skin increases the migration and filopodia formation of skin keratinocytes by activation of FAK/Src pathway. Pol J Food Nutr Sci 2021;71:323-32. https://doi.org/10.31883/pjfns/141515
  15. Sohretoglu D, Huang S. Ganoderma lucidum polysaccharides as an anti-cancer agent. Anticancer Agents Med Chem 2018;18:667-74. https://doi.org/10.2174/1871520617666171113121246
  16. Yang JJ, Wang YH, Yin J, Leng H, Shen SD. Polysaccharides from Ulva prolifera O.F. Muller inhibit cell proliferation via activating MAPK signaling in A549 and H1650 cells. Food Funct 2021;12:6915-24. https://doi.org/10.1039/D1FO00294E
  17. Lee H, Kim JS, Kim E. Fucoidan from seaweed Fucus vesiculosus inhibits migration and invasion of human lung cancer cell via PI3K-Akt-mTOR pathways. PLoS One 2012;7:e50624.
  18. Ryu MJ, Chung HS. Anti-inflammatory activity of fucoidan with blocking NF-kappa B and STAT1 in human keratinocytes cells. Nat Prod Sci 2015;21:205-9.
  19. Sung CJ, Wang HH, Sun KH, Hsieh CC, Huang R, Sun GH, Tang SJ. Fucoidan from Sargassum hemiphyllum inhibits the stemness of cancer stem cells and epithelial-mesenchymal transitions in bladder cancer cells. Int J Biol Macromol 2022;221:623-33. https://doi.org/10.1016/j.ijbiomac.2022.09.047
  20. Ho CH, Chen ML, Huang HL, Lai CJ, Liu CH, Chuu CP, Lin YH. Active targeting of P-selectin by fucoidan modulates the molecular profiling of metastasis in docetaxel-resistant prostate cancer. Mar Drugs 2022;20:542.
  21. Luo J, Li L, Zhu Z, Chang B, Deng F, Wang D, Lu X, Zuo D, Chen Q, Zhou J. Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma. Biomed Pharmacother 2022;154:113602.
  22. Kciuk M, Gielecinska A, Budzinska A, Mojzych M, Kontek R. Metastasis and MAPK pathways. Int J Mol Sci 2022;23:3847.
  23. Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nat Rev Cancer 2014;14:598-610. https://doi.org/10.1038/nrc3792
  24. Jia XB, Zhang Q, Xu L, Yao WJ, Wei L. Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway. Biol Res 2021;54:7.
  25. Zou T, Mao X, Yin J, Li X, Chen J, Zhu T, Li Q, Zhou H, Liu Z. Emerging roles of RAC1 in treating lung cancer patients. Clin Genet 2017;91:520-8. https://doi.org/10.1111/cge.12908
  26. Kyykallio H, Oikari S, Bueno Alvez M, Gallardo Dodd CJ, Capra J, Rilla K. The density and length of filopodia associate with the activity of hyaluronan synthesis in tumor cells. Cancers (Basel) 2020;12:1908.