Advertisement

Journal of Natural Medicines

, Volume 67, Issue 3, pp 519–527 | Cite as

Dieckol, isolated from Ecklonia stolonifera, induces apoptosis in human hepatocellular carcinoma Hep3B cells

  • Jin-Soo Yoon
  • Anandam Kasin Yadunandam
  • Soon-Jin Kim
  • Hee-Chul Woo
  • Hyeung-Rak Kim
  • Gun-Do KimEmail author
Original Paper

Abstract

Phlorotannins have been reported to demonstrate several biological properties, including antioxidant activity, and activities useful in the treatment of diabetic complications and in chemoprevention of several vascular diseases. In this study, we focused on the apoptosis induced by dieckol, a marine algal phlorotannin isolated from Ecklonia stolonifera, on human hepatocellular carcinoma (HCC) Hep3B cells. Dieckol reduced the numbers of viable cells and increased the numbers of apoptotic cells in a dose-dependent manner. Immunoblotting analysis revealed that dieckol increased the expression levels of cleaved caspases-3, 7, 8, and 9, and cleaved poly(ADP-ribose) polymerase. Dieckol increased the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with apoptosis-inducing factor. In addition, dieckol induced increased expression of truncated Bid and Bim. The results indicate that dieckol induces apoptosis via the activation of both death receptor and mitochondrial-dependent pathways in HCC Hep3B cells.

Keywords

Dieckol Ecklonia stolonifera Hepatocellular carcinoma Hep3B Apoptosis 

Notes

Acknowledgments

This work was financially supported by the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRefGoogle Scholar
  2. 2.
    Ho JW, Man K, Sun CK, Lee TK, Poon RT, Fan ST (2005) Effects of a novel immunomodulating agent, FTY720, on tumor growth and angiogenesis in hepatocellular carcinoma. Mol Cancer Ther 4:1430–1438PubMedCrossRefGoogle Scholar
  3. 3.
    Roberts LR (2008) Sorafenib in liver cancer—just the beginning. N Engl J Med 359:420–422PubMedCrossRefGoogle Scholar
  4. 4.
    Roayaie S, Blume IN, Thung SN, Guido M, Fiel MI, Hiotis S, Labow DM, Llovet JM, Schwartz ME (2009) A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 137:850–855PubMedCrossRefGoogle Scholar
  5. 5.
    Newell P, Villanueva A, Llovet JM (2008) Molecular targeted therapies in hepatocellular carcinoma: from pre-clinical models to clinical trials. J Hepatol 49:1–5PubMedCrossRefGoogle Scholar
  6. 6.
    Pang RW, Poon RT (2007) From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. Oncology 72(Suppl 1):30–44PubMedCrossRefGoogle Scholar
  7. 7.
    Varghese L, Agarwal C, Tyagi A, Singh RP, Agarwal R (2005) Silibinin efficacy against human hepatocellular carcinoma. Clin Cancer Res 11:8441–8448PubMedCrossRefGoogle Scholar
  8. 8.
    Kim AR, Shin TS, Lee MS, Park JY, Park KE, Yoon NY, Kim JS, Choi JS, Jang BC, Byun DS, Park NK, Kim HR (2009) Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties. J Agric Food Chem 57:3483–3489PubMedCrossRefGoogle Scholar
  9. 9.
    Ragan MA, Glombitza KW (1986) Phlorotannins, brown algal polyphenols. Prog Phycol Res 4:129–241Google Scholar
  10. 10.
    Zou Y, Qian ZJ, Li Y, Kim MM, Lee SH, Kim SK (2008) Antioxidant effects of phlorotannins isolated from Ishige okamurae in free radical mediated oxidative systems. J Agric Food Chem 56:7001–7009PubMedCrossRefGoogle Scholar
  11. 11.
    Kang KA, Lee KH, Chae S, Koh YS, Yoo BS, Kim JH, Ham YM, Baik JS, Lee NH, Hyun JW (2005) Triphlorethol-A from Ecklonia cava protects V79-4 lung fibroblast against hydrogen peroxide induced cell damage. Free Radic Res 39:883–892PubMedCrossRefGoogle Scholar
  12. 12.
    Kang KA, Lee KH, Park JW, Lee NH, Na HK, Surh YJ, You HJ, Chung MH, Hyun JW (2007) Triphlorethol-A induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor. FEBS Lett 581:2000–2008PubMedCrossRefGoogle Scholar
  13. 13.
    Okada Y, Ishimaru A, Suzuki R, Okuyama T (2004) A new phloroglucinol derivative from the brown alga Eisenia bicyclis: potential for the effective treatment of diabetic complications. J Nat Prod 67:103–105PubMedCrossRefGoogle Scholar
  14. 14.
    Yoon NY, Chung HY, Kim HR, Choi JS (2008) Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera. Fish Sci 74:200–207CrossRefGoogle Scholar
  15. 15.
    Kang K, Park Y, Hwang HJ, Kim SH, Lee JG, Shin HC (2003) Antioxidative properties of brown algae polyphenolics and their perspectives as chemopreventive agents against vascular risk factors. Arch Pharm Res 26:286–293PubMedCrossRefGoogle Scholar
  16. 16.
    Fukuyama Y, Kodama M, Miura I, Kinzyo Z, Mori H, Nakayama Y, Takahashi M (1990) Anti-plasmin inhibitor. Structure of phlorofucofuroeckol A, a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, from Ecklonia kurome Okamura. Chem Pharm Bull 38:133–135PubMedCrossRefGoogle Scholar
  17. 17.
    Ryu BM, Li Y, Qian ZJ, Kim MM, Kim SK (2009) Differentiation of human osteosarcoma cells by isolated phlorotannins is subtly linked to COX-2, iNOS, MMPs, and MAPK signaling: implication for chronic articular disease. Chem Biol Interact 179:192–201PubMedCrossRefGoogle Scholar
  18. 18.
    Joe MJ, Kim SN, Choi HY, Shin WS, Park GM, Kang DW, Kim YK (2006) The inhibitory effects of eckol and dieckol from Ecklonia stolonifera on the expression of matrix metalloproteinase-1 in human dermal fibroblasts. Chem Pharm Bull 29(8):1735–1739CrossRefGoogle Scholar
  19. 19.
    Glombitza KW, Vogels HP (1985) Antibiotics from algae. XXXV Phlorotannins from Ecklonia maxima. Planta Med 51:308–312PubMedCrossRefGoogle Scholar
  20. 20.
    Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:1129–1132PubMedCrossRefGoogle Scholar
  21. 21.
    Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43PubMedCrossRefGoogle Scholar
  22. 22.
    Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371:346–347PubMedCrossRefGoogle Scholar
  23. 23.
    Salvesen GS, Dixit VM (1995) Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell 81:801–809PubMedCrossRefGoogle Scholar
  24. 24.
    Tu H, Jacobs SC, Borkowski A, Kyprianou N (1996) Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta 1 and Bcl-2 expression. Int J Cancer 69:357–363PubMedCrossRefGoogle Scholar
  25. 25.
    Vitale-Cross L, Amornphimoltham P, Fisher G, Molinolo AA, Gutkind JS (2004) Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis. Cancer Res 64:8804–8807PubMedCrossRefGoogle Scholar
  26. 26.
    Tian Z, Pan R, Chang Q, Si J, Xiao P, Wu E (2007) Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via cell cycle arrest and apoptosis. J Ethnopharmacol 114:227–233PubMedCrossRefGoogle Scholar
  27. 27.
    Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4:139–163PubMedCrossRefGoogle Scholar
  28. 28.
    Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308PubMedCrossRefGoogle Scholar
  29. 29.
    Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656PubMedCrossRefGoogle Scholar
  30. 30.
    Breckenridge DG, Xue D (2004) Regulation of mitochondrial membrane permeabilization by BCL-2 family proteins and caspases. Curr Opin Cell Biol 16:647–652PubMedCrossRefGoogle Scholar
  31. 31.
    Bouillet P, Zhang LC, Huang DC, Webb GC, Bottema CD, Shore P, Eyre HJ, Sutherland GR, Adams JM (2001) Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim. Mamm Genome 12(2):163–168PubMedCrossRefGoogle Scholar
  32. 32.
    Deng J, Shimamura T, Perera S, Carlson NE, Cai D, Shapiro GI, Wong KK, Letai A (2007) Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res 67:11867–11875PubMedCrossRefGoogle Scholar
  33. 33.
    Rasheva VI, Domingos PM (2009) Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 14:996–1007PubMedCrossRefGoogle Scholar
  34. 34.
    Candé C, Cecconi F, Dessen P, Kroemer G (2002) Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? J Cell Sci 115:4727–4734PubMedCrossRefGoogle Scholar
  35. 35.
    Antonsson B, Martinou JC (2000) The Bcl-2 protein family. Exp Cell Res 256:50–57PubMedCrossRefGoogle Scholar
  36. 36.
    Heo SJ, Ko SC, Cha SH, Kang DH, Park HS, Choi YU, Kim DK, Jung WK, Jeon YJ (2009) Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation. Toxicol In Vitro 23:1123–1130PubMedCrossRefGoogle Scholar
  37. 37.
    Twist EM, Clark HF, Aden DP, Knowles BB, Plotkin SA (1981) Integration pattern of hepatitis B virus DNA sequences in human hepatoma cell lines. J Virol 37(1):239–243PubMedGoogle Scholar
  38. 38.
    Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV (1998) Immune pathogenesis of hepatocellular carcinoma. J Exp Med 188(2):341–350PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2012

Authors and Affiliations

  • Jin-Soo Yoon
    • 1
  • Anandam Kasin Yadunandam
    • 1
  • Soon-Jin Kim
    • 1
  • Hee-Chul Woo
    • 2
  • Hyeung-Rak Kim
    • 3
  • Gun-Do Kim
    • 1
    Email author
  1. 1.Department of Microbiology, College of Natural SciencesPukyong National UniversityBusanKorea
  2. 2.Division of Applied Chemical Engineering, College of EngineeringPukyong National UniversityBusanKorea
  3. 3.Department of Food Science and Nutrition, College of Fishery SciencesPukyong National UniversityBusanKorea

Personalised recommendations