The Korean Journal of Food And Nutrition (한국식품영양학회지)

The Korean Society of Food and Nutrition (한국식품영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Fucoidan, a Sulfur-Containing Polysaccharide, on Cytotoxicity and Apoptosis in HT-29 Human Colorectal Cancer Cells

함유황 다당체 Fucoidan의 인체 대장암세포(HT-29) 사멸과 Apoptosis에 미치는 영향

  • Kim, Min Ji (Dept. of Food and Nutrition, College of Science and Technology, Duksung Women's University) ;
  • Chung, Ha Sook (Dept. of Food and Nutrition, College of Science and Technology, Duksung Women's University)
  • 김민지 (덕성여자대학교 과학기술대학 식품영양학과) ;
  • 정하숙 (덕성여자대학교 과학기술대학 식품영양학과)
  • Received : 2022.03.18
  • Accepted : 2022.06.12
  • Published : 2022.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The purpose of this study was to investigate the biological activity of fucoidan, a sulfur-containing polysaccharide, on cytotoxicity and apoptosis in the human HT-29 colorectal cancer cell line using cell viability, Flow cytometry, Western blot, and RT-PCR analyses. Fucoidan inhibited the proliferation of HT-29 cells by 39.6% at a concentration of 100 ㎍/mL for 72 h. The inhibition was dose-dependent and accompanied by apoptosis. Flow cytometric analysis showed that fucoidan increased early apoptosis and late apoptosis by 65.84% and 72.09% at concentrations of 25 and 100 ㎍/mL, respectively. Analysis of the mechanism of these events indicated that fucoidan-treated cells exhibited increases in the activation of caspase-3, caspase-8, and PARP in a dose-dependent manner. These results suggest that fucoidan may inhibit the growth of human colorectal cancer cells by various apoptosis-promoting effects, as well as by apoptosis itself.

Keywords

References

  1. Baetu TM, Hiscott J. 2002. On the TRAIL to apoptosis. Cytokine Growth Factor Rev 13:199-207 https://doi.org/10.1016/S1359-6101(02)00006-0
  2. Bai X, Wang Y, Hu B, Cao Q, Xing M, Song S, Ji A. 2020. Fucoidan induces apoptosis of HT-29 cells via the activation of DR4 and mitochondrial pathway. Mar Drugs 18:220 https://doi.org/10.3390/md18040220
  3. Bilan MI, Grachev AA, Ustuzhanina NE, Shashkov AS, Nifantiev NE, Usov AI. 2002. Structure of a fucoidan from the brown seaweed Fucus evanescens C. Ag. Carbohydr Res 337:719-730 https://doi.org/10.1016/S0008-6215(02)00053-8
  4. Brunner G, Reimbold K, Meissauer A, Schirrmacher V, Erkell LJ. 1998. Sulfated glycosaminoglycans enhance tumor cell invasion in vitro by stimulating plasminogen activation. Exp Cell Res 239:301-310 https://doi.org/10.1006/excr.1997.3877
  5. Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res 47:936-942
  6. Chai F, Truong-Tran AQ, Ho LH, Zalewski PD. 1999. Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol Cell Biol 77:272-278 https://doi.org/10.1046/j.1440-1711.1999.00825.x
  7. Chevolot L, Foucault A, Chaubet F, Kervarec N, Sinquin C, Fisher AM, Boisson-Vidal C. 1999. Further data on the structure of brown seaweed fucans: Relationships with anticoagulant activity. Carbohydr Res 319:154-165 https://doi.org/10.1016/S0008-6215(99)00127-5
  8. Chevolot L, Mulloy B, Ratiskol J, Foucault A, Colliec-Jouault S. 2001. A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae. Carbohydr Res 330:529-535 https://doi.org/10.1016/S0008-6215(00)00314-1
  9. Chiarugi V, Magnelli L, Cinelli M, Basi G. 1994. Apoptosis and the cell cycle. Cell Mol Biol Res 40:603-612
  10. Chizhov AO, Dell A, Morris HR, Haslam SM, McDowell RA, Shashkov AS, Nifant'ev NE, Khatuntseva EA, Usov AI. 1999. A study of fucoidan from the brown seaweed Chorda filum. Carbohydr Res 320:108-119 https://doi.org/10.1016/S0008-6215(99)00148-2
  11. Cho BO, Ryu HW, So YK, Jin CH, Byun MW, Kim WG, Jeong IY. 2012. Ishige sinicola extracts induce apoptosis via activation of a caspase cascade in human HeLa cells. J Korean Soc Food Sci Nutr 41:901-906 https://doi.org/10.3746/JKFN.2012.41.7.901
  12. Choi JH, Kim HI, Lee IS. 2009. Effect of Rosmarinus officinalis L. on growth inhibition and apoptosis induction in cancer cells. J Korean Soc Food Sci Nutr 38:1008-1015 https://doi.org/10.3746/JKFN.2009.38.8.1008
  13. Daub CD, Mabate B, Malgas S, Pletschke BI. 2020. Fucoidan from Ecklonia maxima is a powerful inhibitor of the diabetes-related enzyme, α-glucosidase. Int J Biol Macromol 151:412-420 https://doi.org/10.1016/j.ijbiomac.2020.02.161
  14. Debatin KM. 2004. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother 53:153-159 https://doi.org/10.1007/s00262-003-0474-8
  15. DelBigio MR, Yan HJ, Campbell TM, Peeling J. 1999. Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats. Neurol Res 21:415-419 https://doi.org/10.1080/01616412.1999.11740953
  16. Dimitrova-Shumkovska J, Krstanoski L, Veenman L. 2020. Potential beneficial actions of Fucoidan in brain and liver injury, disease, and intoxication-potential implication of sirtuins. Mar Drugs 18:242 https://doi.org/10.3390/md18050242
  17. Fernando IPS, Dias MKHM, Madusanka DMD, Han EJ, Kim MJ, Jeon YJ, Ahn G. 2020. Fucoidan refined by Sargassum confusum indicate protective effects suppressing photo-oxidativestress and skin barrier perturbation in UVB-induced human keratinocytes. Int J Biol Macromol 164:149-161 https://doi.org/10.1016/j.ijbiomac.2020.07.136
  18. Fitton JH, Park AY, Karpiniec SS, Stringer DN. 2021. Fucoidan and lung function: Value in viral infection. Mar Drugs 19:4
  19. Galluzzi L, Kepp O, Trojel-Hansen C, Kroemer G. 2012. Mitochondrial control of cellular life, stress, and death. Circ Res 111:1198-1207 https://doi.org/10.1161/CIRCRESAHA.112.268946
  20. Guon TE, Chung HS. 2016. Induction of apoptosis with Kigelia africana fruits in HCT116 human colon cancer cells via MAPKs signaling pathway. Nat Prod Sci 22:209-215 https://doi.org/10.20307/nps.2016.22.3.209
  21. Guon TE, Chung HS. 2017. Moringa oleifera fruit induce apoptosis via reactive oxygen species-dependent activation of mitogen-activated protein kinases in human melanoma A2058 cells. Oncol Lett 14:1703-1710 https://doi.org/10.3892/ol.2017.6288
  22. Haupt S, Berger M, Goldberg Z, Haupt Y. 2003. Apoptosis - the p53 network. J Cell Sci 116:4077-4085 https://doi.org/10.1242/jcs.00739
  23. Hu W, Kavanagh JJ. 2003. Anticancer therapy targeting the apoptotic pathway. Lancet Oncol 4:721-729 https://doi.org/10.1016/S1470-2045(03)01277-4
  24. Huang J, Huang J, Li Y, Lv H, Yin T, Fan S, Zhang C, Li H. 2021. Fucoidan protects against high-fat diet-induced obesity and modulates gut microbiota in institute of cancer research mice. J Med Food 24:1058-1067 https://doi.org/10.1089/jmf.2021.K.0030
  25. Jaattela M. 2002. Programmed cell death: Many ways for cells to die decently. Ann Med 34:480-488 https://doi.org/10.1080/078538902321012423
  26. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. 2005. Cancer statistics, 2005. CACancer J Clin 55:10-30 https://doi.org/10.3322/canjclin.55.1.10
  27. Jiang Z, Okimura T, Yokose T, Yamasaki Y, Yamaguchi K, Oda T. 2010. Effects of sulfated fucan, ascophyllan, from the brown Alga Ascophyllum nodosum on various cell lines: A comparative study on ascophyllan and fucoidan. J Biosci Bioeng 110:113-117 https://doi.org/10.1016/j.jbiosc.2010.01.007
  28. Kim KJ, Lee OH, Lee BY. 2010. Fucoidan, a sulfated polysaccharide, inhibits adipogenesis through the mitogen-activated protein kinase pathway in 3T3-L1 preadipocytes. Life Sci 86:791-797 https://doi.org/10.1016/j.lfs.2010.03.010
  29. Kim R, Emi M, Tanabe K. 2005. Caspase-dependent and -independent cell death pathways after DNA damage. Oncol Rep 14:595-599
  30. Korsmeyer SJ. 1995. Regulators of cell death. Trends Genet 11:101-105 https://doi.org/10.1016/S0168-9525(00)89010-1
  31. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. 1996. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 348:1467-1471 https://doi.org/10.1016/S0140-6736(96)03430-7
  32. LeBlanc HN, Ashkenazi A. 2003. Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10:66-75 https://doi.org/10.1038/sj.cdd.4401187
  33. Lee KH, Rhee KH. 2014. Conversion effect to cotinine from nicotine by Fucoidan. Korean J Food Nutr 27:725-731 https://doi.org/10.9799/KSFAN.2014.27.4.725
  34. Lee YR. 2013. Antioxidative and anticancer activities of Xanthium strumarium extracts prepared from different parts. Korean J Food Nutr 26:609-614 https://doi.org/10.9799/KSFAN.2013.26.4.609
  35. Li J, Guo C, Wu J. 2020. Fucoidan: Biological activity in liver diseases. Am J Clin Med 48:1617-1632 https://doi.org/10.1142/S0192415X20500809
  36. Mabate B, Daub CD, Malgas S, Edkins AL, Pletschke BI. 2021. Fucoidan structure and its impact on glucose metabolism: Implications for diabetes and cancer therapy. Mar Drugs 19:30 https://doi.org/10.3390/md19010030
  37. Ministry of Health and Welfare. 2021. 2019 Cancer registration statistics. Available from https://www.mohw.go.kr/react/al/sal0301vw.jsp?PAR_MENU_ID=04&MENU_ID=0403&page=1&CONT_SEQ=369164 [cited 20 April 2021]
  38. Mustafa S, Pawar JS, Ghosh I. 2021. Fucoidan induces ROS-dependent epigenetic modulation in cervical cancer HeLa cell. Int J Biol Macromol 181:180-192 https://doi.org/10.1016/j.ijbiomac.2021.03.110
  39. Na E, Lee JW, Lim SY. 2019. Proximate analysis, fatty acid composition of Lycopus lucidus Turcz. and its cytotoxic effect in cancer cell lines. Korean J Food Nutr 32:208-215 https://doi.org/10.9799/KSFAN.2019.32.3.208
  40. Nicholson DW, Thornberry NA. 1997. Caspases: Killer proteases. Trends Biochem Sci 22:299-306 https://doi.org/10.1016/S0968-0004(97)01085-2
  41. Nishino T, Nishioka C, Ura H, Nagumo T. 1994. Isolation and partial characterization of a noval amino sugar-containing fucan sulfate from commercial Fucus vesiculosus fucoidan. Carbohydr Res 255:213-224 https://doi.org/10.1016/S0008-6215(00)90980-7
  42. Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, Capaccioli S. 2009. Natural compounds for cancer treatment and prevention. Pharmacol Res 59:365-378 https://doi.org/10.1016/j.phrs.2009.01.017
  43. Paoluzzi L, O'Connor OA. 2010. Targeting survival pathways in lymphoma. Adv Exp Med Biol 687:79-96 https://doi.org/10.1007/978-1-4419-6706-0_5
  44. Piao XL, Park IH, Baek SH, Kim HY, Park MK, Park JH. 2004. Antioxidative activity of furanocoumarins isolated from Angelicae dahuricae. J Ethnopharmacol 93:243-246 https://doi.org/10.1016/j.jep.2004.03.054
  45. Reed JC. 2002. Apoptosis-based therapies. Nat Rev Drug Discov 1:111-121 https://doi.org/10.1038/nrd726
  46. Ryu MJ, Chung HS. 2011. Effects on hot water extract of Schizandra chinensis on colon cancer cell line. Food Eng Prog 15:64-69
  47. Ryu MJ, Chung HS. 2015. [10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells. In Vitro Cell Dev Biol Anim 51:92-101 https://doi.org/10.1007/s11626-014-9806-6
  48. Ryu MJ, Chung HS. 2016. Fucoidan reduces oxidative stress by regulating the gene expression of HO-1 and SOD-1 through the Nrf2/ERK signaling pathway in HaCaT cells. Mol Med Rep 14:3255-3260 https://doi.org/10.3892/mmr.2016.5623
  49. Ryu MJ, Kim AD, Kang KA, Chung HS, Kim HS, Suh IS, Chang WY, Hyun JW. 2013. The green algae Ulva fasciata Delile extract induces apoptotic cell death in human colon cancer cells. In Vitro Cell Dev Biol Anim 49:74-81 https://doi.org/10.1007/s11626-012-9547-3
  50. Ryu YS, Hyun JW, Chung HS. 2020. Fucoidan induces apoptosis in A2058 cells through ROS-exposed activation of MAPKs signaling pathway. Nat Prod Sci 26:191-199 https://doi.org/10.20307/nps.2020.26.3.191
  51. Selvakumar P, Sharma RK. 2007. Role of calpain and caspase system in the regulation of N-myristoyltransferase in human colon cancer. Int J Mol Med 19:823-827
  52. Shin MK, Byun JS. 2004. The anti-tumor effect of Soonkiwhajungtang with doxorubicin in MKN-45 conclusion. J Korean Orient Med 25:98-109
  53. Smith ML, Ford JM, Hollander MC, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC, Fornace AJ Jr. 2000. p53-mediated DNA repair responses to UV radiation: Studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol Cell Biol 20:3705-3714 https://doi.org/10.1128/MCB.20.10.3705-3714.2000
  54. Suprunchuk V. 2021. Ultrasonic-treated fucoidan as a promising therapeutic agent. Polim Med 51:85-90 https://doi.org/10.17219/pim/143961
  55. Tan ML, Ooi JP, Ismail N, Moad AIH, Muhammad TST. 2009. Programmed cell death pathways and current antitumor targets. Pharm Res 26:1547-1560 https://doi.org/10.1007/s11095-009-9895-1
  56. Torzsas TL, Kendall CWC, Sugano M, Iwamoto Y, Rao AV. 1996. The influence of high and low molecular weight chitosan on colonic cell proliferation and aberrant crypt foci development in CF1 mice. Food Chem Toxicol 34:73-77 https://doi.org/10.1016/0278-6915(95)00083-6
  57. Trauzold A, Wermann H, Arlt A, Schutze S, Schafer H, Oestern S, Roder C, Ungefroren H, Lampe E, Heinrich M, Walczak H, Kalthoff H. 2001. CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-κB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells. Oncogene 20:4258-4269 https://doi.org/10.1038/sj/onc/1204559
  58. Tsang WP, Kwok TT. 2008. Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis 13:1215-1222 https://doi.org/10.1007/s10495-008-0256-z
  59. van Weelden G, Bobinski M, Okla K, van Weelden WJ, Romano A, Pijnenborg JMA. 2019. Fucoidan structure and activity in relation to anti-cancer mechanisms. Mar Drugs 17:32 https://doi.org/10.3390/md17010032
  60. Vogelstein B, Lane D, Levine AJ. 2000. Surfing the p53 network. Nature 408:307-310 https://doi.org/10.1038/35042675
  61. Winawer SJ, St John DJ, Bond JH, Rozen P, Burt RW, Waye JD, Kronborg O, O'Brien MJ, Bishop DT, Kurtz RC, Shike M, Swaroop SV, Levin B, Fruhmorgen P, Lynch HT. 1996. Prevention of colorectal carcinoma. Current WHO guidelines for early detection of colorectal carcinoma. World Health Organization Collaborating Center for the prevention of colorectal cancer. Leber Magen Darm 26:139-140, 143
  62. Xue M, Ji X, Liang H, Liu Y, Wang B, Sun L, Li W. 2018. The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer. Food Funct 9:1214-1223 https://doi.org/10.1039/C7FO01677H
  63. Yoon YS, Yu CS, Jung SH, Choi PW, Han KR, Kim HC, Kim JC. 2007. Characteristics of colorectal cancer detected at the health promotion center. J Korean Soc Coloproctol 23:321-326 https://doi.org/10.3393/jksc.2007.23.5.321
  64. Youle RJ, Strasser A. 2008. The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47-59 https://doi.org/10.1038/nrm2308
  65. Yu C, Lin F, Guo H, Liu G, He X, Wen X. 2021. Dietary fucoidan extracted from macroalgae Saccharina japonica alleviate the hepatic lipid accumulation of black seabream (Acanthopagrus schlegelii). Food Funct 12:12724-12733 https://doi.org/10.1039/D1FO03490A
  66. Zhao LP, Kushi LH, Klein RD, Prentice RL. 1991. Quantitative review of studies of dietary fat and rat colon carcinoma. Nutr Cancer 15:169-177 https://doi.org/10.1080/01635589109514124
  67. Zhu Y, Liu L, Sun Z, Ji Y, Wang D, Mei L, Shen P, Li Z, Tang S, Zhang H, Zhou Q, Deng J. 2021. Fucoidan as a marine-origin prebiotic modulates the growth and antibacterial ability of Lactobacillus rhamnosus. Int J Biol Macromol 180:599-607 https://doi.org/10.1016/j.ijbiomac.2021.03.065