Skip to main content
Log in

Antiproliferative activity of sulfated polysaccharide isolated from an enzymatic digest of Ecklonia cava on the U-937 cell line

  • Published:
Journal of Applied Phycology Aims and scope Submit manuscript

Abstract

A sulfated polysaccharide purified from a brown alga Ecklonia cava, having high anticoagulant activity was investigated for its antiproliferative effect on murine colon carcinoma (CT-26), human leukemic monocyte lymphoma (U-937), human promyelocytic leukemia (HL-60), and mouse melanoma (B-16) cell lines. The sulfated polysaccharide isolated and purified from an enzymatic extract of E. cava had a good selective tumor cell growth inhibition effect; its effect on HL-60 and U-937 was especially promising. The IC50 value for the sulfated polysaccharide from E. cava (ECSP) on U-937 was 43.9 μg mL−1. The presence of the sample in the cell culture media stimulated the induction of apoptosis, revealed by nuclear staining with Hoechst 33342. The apoptosis induction was confirmed by the cell cycle analysis, while pronounced sub-G1 phase arrests of 9.5% and 13.8% were also clearly observed when the cells were treated at 15 and 30 μg mL−1 of ECSP in the U-937 cell line, respectively. After a 24-h incubation period, ECSP dose-dependently enhanced the DNA fragmentation on the U-937 cell line as observed in the agarose gel electrophoresis assay. To rule out the action mechanism of ECSP for its anticancer activity, some western blot analyses were conducted with several antibodies (caspase-7, caspase-8, Bax, Bcl-xL, and PARP) and ECSP had a clear effect on the caspase -7 and 8 which cleave protein substrates, including PARP, an inducer of apoptosis responsible for DNA cleavage. Moreover, ECSP controlled the cellular transmembrane molecules like Bax and Bcl-xL. Taken together, the above results demonstrate that the apoptosis for antiproliferative effect of ECSP was clearly induced on U-937 cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ahn GN, Kim KN, Cha SH, Song CB, Lee J, Heo MS et al (2007) Antioxidant activities of phlorotannins purified from Ecklonia cava on free radical scavenging using ESR and H2O2-mediated DNA damage. Eur Food Res Technol 226:71–79 doi:10.1007/s00217-006-0510-y

    Article  CAS  Google Scholar 

  • Asia Y, Miyakawa Y, Nakazatao T, Shibata H, Saito K, Ikeda Y et al (2005) Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways. Am J Hematol 78:7–14 doi:10.1002/ajh.20182

    Article  CAS  Google Scholar 

  • Athukorala Y, Jung WK, Vasanthan T, Jeon YJ (2006) An anticoagulative polysaccharide from an enzymatic hydrolysate of Ecklonia cava. Carbohydr Polym 66:84–191 doi:10.1016/j.carbpol.2006.03.002

    Article  CAS  Google Scholar 

  • Cavas L, Baskin Y, Yurdakoc K, Olgum N (2006) Antiproliferative and newly attributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea. J Exp Mar Biol Ecol 339:111–119 doi:10.1016/j.jembe.2006.07.019

    Article  Google Scholar 

  • Gschwind M, Huber G (1995) Apoptotic cell death induced by β-amyloid 1–42 peptide is cell type dependent. J Neurochem 65:292–300

    PubMed  CAS  Google Scholar 

  • Jung WK, Athukorala Y, Lee YJ, Cha SH, Lee CH, Vasanthan T et al (2007) Sulfated polysaccharide purified from Ecklonia cava accelerates antithrombin III-mediated plasma proteinase inhibition. J Appl Phycol 19:425–430 doi:10.1007/s10811-006-9149-0

    Article  CAS  Google Scholar 

  • Kim KN, Lee KW, Song CB, Jeon YJ (2006a) Cytotoxic activities of green and brown seaweeds collected from Jeju Island against four tumor cell lines. J Food Sci Nutr 11:17–24

    Google Scholar 

  • Kim KN, Lee KW, Song CB, Ahn CB, Jeon YJ (2006b) Cytotoxic activities of red algae collected from Jeju Island against four tumor cell lines. J Food Sci Nutr 11:177–183

    Article  Google Scholar 

  • Kuda T, Taniguchi E, Nishizawa M, Araki Y (2002) Fate of water-soluble polysaccharides in dried Chorda filum, a brown alga during water washing. J Food Compost Anal 15:3–9 doi:10.1006/jfca.2001.1037

    Article  CAS  Google Scholar 

  • Lizard G, Fournel S, Genestier L, Dhedin N, Chaput C, Flacher M et al (1995) Kinetics of plasma membrane and mitochondrial alterations in the cells undergoing apoptosis. Cytometry 21:275–283 doi:10.1002/cyto.990210308

    Article  PubMed  CAS  Google Scholar 

  • Mans DRA, Rocha AB, Schwavtsann G (2000) Anti-cancer drug discovery and development in Brazil: targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds. Oncology 5:185–198

    Article  CAS  Google Scholar 

  • Matsubara K (2004) Recent advances in marine algal anticoagulants. Curr Med Chem Cardiovasc Hematol Agents 2:13–19 doi:10.2174/1568016043477314

    Article  PubMed  CAS  Google Scholar 

  • Matsuda M, Yamori T, Naitoh M, Okutani K (2003) Structural revision of sulfated polysaccharide B-1 isolated from a marine Pseudomonas species and Its cytotoxic activity against human cancer cell lines. Mar Biotechnol 5:13–19 doi:10.1007/s10126-002-0046-5

    Article  PubMed  CAS  Google Scholar 

  • Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63 doi:10.1016/0022-1759(83)90303-4

    Article  Google Scholar 

  • Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271–279 doi:10.1016/0022-1759(91)90198-O

    Article  PubMed  CAS  Google Scholar 

  • Park HY, Lim CW, Kim YK, Yoon HD, Lee KJ (2006) Immunostimulating and anticancer activities of hot water extract from Capsosiphon fulvescens. J Korean Soc Appl Biol Chem 49:343–348

    Google Scholar 

  • Teruya T, Konishi T, Uechi S, Tamaki H, Tako M (2007) Anti-proliferative activity of oversulfated fucoidan from commercially cultured Cladosiphon okamuranus TOKIDA in U-937 cells. Int J Biol Macromol 41:221–226. doi:10.1016/j.ibiomac.2007.02.010

    Article  PubMed  CAS  Google Scholar 

  • Wang XW, Zhan Q, Coursen JD, Khan MA, Kontny HU, Yu L et al (1999) GADD45 induction of a G2/M cell cycle checkpoint. Proc Natl Acad Sci USA 96:3706–3711 doi:10.1073/pnas.96.7.3706

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto I, Takahashi M, Suzuki T, Seino H, Mori H (1984) Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum. Jap J Exp Med 54:143−151

    PubMed  CAS  Google Scholar 

  • Ye J, Li Y, Teruya K, Katakura Y, Ichikawa A, Eto H et al (2005) Enzyme-digested fucoidan extracts derived from seaweed Mozuku of Cladosiphon novae-caledoniae Kylin inhibit invasion and angiogenesis of tumor cells. Cytotechnology 47:117–126 doi:10.1007/s10616-005-3761-8

    Article  PubMed  Google Scholar 

  • Zhang CX, Huang KX (2005) Apoptosis induction on HL-60 cells of a novel polysaccharide from the mucus of the loach, Misgurnus anguillicaudatus. J Ethnopharmacol 99:385–390 doi:10.1016/j.jep.2005.02.033

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This research was supported by a grant (M2007-03) from Marine Bioprocess Research Center of the Marine Bio 21 Center funded by the Ministry of Maritime Affairs & Fisheries, Republic of Korea.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to You-Jin Jeon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Athukorala, Y., Ahn, G.N., Jee, YH. et al. Antiproliferative activity of sulfated polysaccharide isolated from an enzymatic digest of Ecklonia cava on the U-937 cell line. J Appl Phycol 21, 307–314 (2009). https://doi.org/10.1007/s10811-008-9368-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10811-008-9368-7

Keywords

Navigation