In Vitro and In Vivo Effects of Ulvan Polysaccharides from .

Jorge García-Márquez, Bruna Rodrigues Moreira, Piedad Valverde-Guillén, Sofía Latorre-Redoli, Candela T Caneda-Santiago, Gabriel Acién, Eduardo Martínez-Manzanares, Manuel Marí-Beffa, Roberto T Abdala-Díaz
Author Information
  1. Jorge García-Márquez: Department of Microbiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain. ORCID
  2. Bruna Rodrigues Moreira: Phycology Laboratory, Department of Botany, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil. ORCID
  3. Piedad Valverde-Guillén: Department of Cell Biology, Genetics and Physiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain. ORCID
  4. Sofía Latorre-Redoli: Department of Cell Biology, Genetics and Physiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain. ORCID
  5. Candela T Caneda-Santiago: Department of Cell Biology, Genetics and Physiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain.
  6. Gabriel Acién: Department of Chemical Engineering, Almería University, 04120 Almería, Spain. ORCID
  7. Eduardo Martínez-Manzanares: Department of Microbiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain. ORCID
  8. Manuel Marí-Beffa: Department of Cell Biology, Genetics and Physiology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain.
  9. Roberto T Abdala-Díaz: Department of Ecology and Geology, Faculty of Science, Andalusian Institute of Blue Biotechnology and Development (IBYDA), Malaga University, Campus Universitario de Teatinos s/n, 29071 Malaga, Spain.

Abstract

One of the main bioactive compounds of interest from the species is the sulfated polysaccharide ulvan, which has recently attracted attention for its anticancer properties. This study investigated the cytotoxic activity of ulvan polysaccharides obtained from in the following scenarios: (i) in vitro against healthy and carcinogenic cell lines (1064sk (human fibroblasts), HACAT (immortalized human keratinocytes), U-937 (a human leukemia cell line), G-361 (a human malignant melanoma), and HCT-116 (a colon cancer cell line)) and (ii) in vivo against zebrafish embryos. Ulvan exhibited cytotoxic effects on the three human cancer cell lines tested. However, only HCT-116 demonstrated sufficient sensitivity to this ulvan to make it relevant as a potential anticancer treatment, presenting an LC of 0.1 mg mL. The in vivo assay on the zebrafish embryos showed a linear relationship between the polysaccharide concentration and growth retardation at 7.8 hpf mL mg, with an LC of about 5.2 mg mL at 48 hpf. At concentrations near the LC, toxic effects, such as pericardial edema or chorion lysis, could be found in the experimental larvae. Our in vitro study supports the potential use of polysaccharides extracted from as candidates for treating human colon cancer. However, the in vivo assay on zebrafish indicated that the potential use of ulvan as a promising, safe compound should be limited to specific concentrations below 0.001 mg mL since it revealed side effects on the embryonic growth rate and osmolar balance.

Keywords

References

  1. Carbohydr Polym. 2020 Nov 15;248:116783 [PMID: 32919571]
  2. Carbohydr Polym. 2014 Jan;99:365-71 [PMID: 24274519]
  3. Int J Dev Biol. 2011;55(4-5):505-9 [PMID: 21858773]
  4. Mar Drugs. 2020 Oct 26;18(11): [PMID: 33114784]
  5. Fish Shellfish Immunol. 2020 Dec;107(Pt A):414-425 [PMID: 33038507]
  6. Dev Dyn. 1995 Jul;203(3):253-310 [PMID: 8589427]
  7. Int Immunopharmacol. 2009 Mar;9(3):324-9 [PMID: 19159698]
  8. Signal Transduct Target Ther. 2021 May 31;6(1):201 [PMID: 34054126]
  9. Chem Res Toxicol. 2020 Jan 21;33(1):95-118 [PMID: 31625720]
  10. Compr Rev Food Sci Food Saf. 2019 May;18(3):817-831 [PMID: 33336929]
  11. Drug Des Devel Ther. 2016 Dec 28;11:103-121 [PMID: 28096658]
  12. Int J Mol Sci. 2021 Feb 07;22(4): [PMID: 33562361]
  13. Mar Drugs. 2020 Nov 07;18(11): [PMID: 33171870]
  14. Front Pharmacol. 2018 Aug 06;9:777 [PMID: 30127738]
  15. Int J Biol Macromol. 2016 Dec;93(Pt A):695-702 [PMID: 27637450]
  16. Drug Discov Today. 2018 Feb;23(2):434-447 [PMID: 29107095]
  17. Prog Mol Biol Transl Sci. 2014;124:93-122 [PMID: 24751428]
  18. Asian Pac J Trop Med. 2016 Dec;9(12):1200-1211 [PMID: 27955748]
  19. Int J Biol Macromol. 2013 Nov;62:155-61 [PMID: 23994786]
  20. Mar Drugs. 2016 Feb 25;14(3): [PMID: 26927134]
  21. Int J Nanomedicine. 2011;6:3351-9 [PMID: 22267920]
  22. Drug Discov Today. 2018 Feb;23(2):366-374 [PMID: 29081356]
  23. Int J Biol Macromol. 2019 Jun 15;131:614-623 [PMID: 30898597]
  24. ACS Appl Mater Interfaces. 2016 Jan 27;8(3):1707-17 [PMID: 26710937]
  25. Mol Biol Rep. 2022 Aug;49(8):7425-7435 [PMID: 35716287]
  26. Carbohydr Polym. 2019 Jan 1;203:441-449 [PMID: 30318233]
  27. Heliyon. 2021 Feb 04;7(2):e06003 [PMID: 33598573]
  28. Clin Pharmacol Ther. 2007 Jul;82(1):70-80 [PMID: 17495877]
  29. Carbohydr Polym. 2021 Oct 15;270:118365 [PMID: 34364610]
  30. J Hazard Mater. 2020 Aug 5;395:122621 [PMID: 32289630]
  31. Carbohydr Polym. 2020 May 1;235:115929 [PMID: 32122475]
  32. Int J Biol Macromol. 2017 Dec;105(Pt 2):1430-1439 [PMID: 28754621]
  33. Carbohydr Polym. 2020 Oct 1;245:116469 [PMID: 32718604]
  34. Int J Oncol. 2019 Feb;54(2):407-419 [PMID: 30570109]
  35. Clin Epigenetics. 2019 Feb 11;11(1):25 [PMID: 30744689]
  36. Chem Rev. 2021 Mar 24;121(6):3352-3389 [PMID: 33152247]
  37. Pigment Cell Melanoma Res. 2012 Mar;25(2):131-43 [PMID: 22252091]
  38. Curr Opin Genet Dev. 2000 Jun;10(3):252-6 [PMID: 10826982]
  39. CA Cancer J Clin. 2021 Jan;71(1):7-33 [PMID: 33433946]
  40. Int J Biol Macromol. 2018 Feb;107(Pt A):803-807 [PMID: 28962845]
  41. Breast Cancer (Dove Med Press). 2017 Feb 27;9:67-83 [PMID: 28280387]
  42. Sci Rep. 2021 Nov 29;11(1):23079 [PMID: 34845290]
  43. Mar Biotechnol (NY). 2016 Apr;18(2):264-70 [PMID: 26838966]
  44. Int J Biol Macromol. 2020 May 1;150:102-113 [PMID: 32044370]
  45. Biomed Pharmacother. 2018 May;101:458-477 [PMID: 29501768]
  46. Dev Biol. 2001 Feb 15;230(2):278-301 [PMID: 11161578]
  47. Environ Res. 2022 Oct;213:113655 [PMID: 35716813]
  48. Fish Shellfish Immunol. 2007 Oct;23(4):901-5 [PMID: 17442590]
  49. Mar Biotechnol (NY). 2019 Aug;21(4):577-587 [PMID: 31250232]
  50. Sci Rep. 2020 Apr 9;10(1):6132 [PMID: 32273578]
  51. Methods Mol Biol. 2017;1641:325-333 [PMID: 28748473]
  52. Carbohydr Polym. 2019 Aug 15;218:355-370 [PMID: 31221340]
  53. Front Genet. 2021 Aug 05;12:675331 [PMID: 34490030]
  54. Pharmacol Res. 2021 Jan;163:105320 [PMID: 33271295]
  55. J Microbiol Biotechnol. 2019 Aug 28;29(8):1204-1211 [PMID: 31336432]
  56. Expert Opin Drug Discov. 2017 Apr;12(4):379-389 [PMID: 28277839]
  57. Fish Shellfish Immunol. 2019 Dec;95:399-410 [PMID: 31654769]
  58. Carbohydr Polym. 2021 Jun 1;261:117879 [PMID: 33766366]
  59. Int J Biol Macromol. 2017 Nov;104(Pt A):1185-1193 [PMID: 28690171]
  60. J Nat Prod. 1993 Apr;56(4):478-88 [PMID: 7684438]
  61. Integr Cancer Ther. 2015 Nov;14(6):525-45 [PMID: 26130745]
  62. Int J Biol Macromol. 2020 Jun 1;152:894-903 [PMID: 32126202]
  63. CA Cancer J Clin. 2018 Nov;68(6):394-424 [PMID: 30207593]
  64. Int J Biol Macromol. 2020 Jan 15;143:724-731 [PMID: 31734360]
  65. Chin Med. 2012 Jun 10;7(1):15 [PMID: 22682026]
  66. J Phycol. 2009 Aug;45(4):962-73 [PMID: 27034227]
  67. Cancer Res. 2007 Dec 1;67(23):11386-92 [PMID: 18056466]
  68. Carbohydr Polym. 2018 Sep 1;195:29-38 [PMID: 29804979]
  69. J Anim Physiol Anim Nutr (Berl). 2021 Nov;105(6):1075-1102 [PMID: 33660883]
  70. Int Immunopharmacol. 2019 Feb;67:98-105 [PMID: 30537636]
  71. Mar Drugs. 2020 Nov 26;18(12): [PMID: 33255947]
  72. Toxics. 2020 Dec 21;8(4): [PMID: 33371320]

Grants

  1. A.1. grants (to S.L.-R.)/University of Malaga
  2. A.1. grants (to C.C.-S.)/University of Malaga
  3. A.1. grants (to P.V.-G.)/University of Malaga
  4. UMA18-FEDERJA-274/Regional Government of Andalusia
  5. CAPES/PRINT process nos. 88887.578926/2020-00 (to B.R.M.)/Coordination for the Improvement of Higher Education Personnel (Brazil)
  6. CAPES 88882.438333/2019-01 (to B.R.M.)/Coordination for the Improvement of Higher Education Personnel (Brazil)

Word Cloud

Created with Highcharts 10.0.0humanulvancellcancerzebrafishmgmLcytotoxicpolysaccharideslinesvivoeffectspotentialLCpolysaccharideanticancerstudyactivityvitrolineHCT-116colonembryosUlvanHowever0assaygrowthhpfconcentrationsuseOnemainbioactivecompoundsinterestspeciessulfatedrecentlyattractedattentionpropertiesinvestigatedobtainedfollowingscenarios:healthycarcinogenic1064skfibroblastsHACATimmortalizedkeratinocytesU-937leukemiaG-361malignantmelanomaiiexhibitedthreetesteddemonstratedsufficientsensitivitymakerelevanttreatmentpresenting1showedlinearrelationshipconcentrationretardation785248neartoxicpericardialedemachorionlysisfoundexperimentallarvaesupportsextractedcandidatestreatingindicatedpromisingsafecompoundlimitedspecific001sincerevealedsideembryonicrateosmolarbalanceVitroVivoEffectsPolysaccharidesUlvarigidaembryotoxicitytest

Similar Articles

Cited By (3)