Skip to main content
SpringerLink
Log in

Anti-cancer Effects of Triterpene Glycosides, Frondoside A and Cucumarioside A2-2 Isolated from Sea Cucumbers

  • Chapter
  • First Online:
Book cover Handbook of Anticancer Drugs from Marine Origin

Abstract

Very low toxicity and various in vitro effects of triterpene glycosides make it a suitable agent for cancer prevention and treatment. The molecular mechanisms of action of marine triterpene glycosides, including Frondoside A and Cucumariosides on the apoptosis of cancer cells are not fully investigated. Frondoside A from sea cucumber Cucumaria frondosa and Cucumariosides from Cucumaria japonica are pentaosides and the main structural difference between Frondoside A and Cucumarioside A2-2 is in the functional group at C-16 of the aglycone (acetoxy or keto group) and the third carbohydrate unit in the carbohydrate chain. They strongly induce apoptosis of leukemic cells but Frondoside A-induced apoptosis is more potent and rapid than Cucumarioside A2-2-induced apoptosis. The effects of Frondoside A and A2-2 for cell death-inducing capability can be compared with attention paid to structure-activity relationships. In this review, the differential effects of Frondoside A and Cucumarioside on the apoptosis of leukemic cells are discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nigrelli RF (1952) The effects of holothurin on fish and mice with sarcoma-180. Zoologica 37:89–90

    CAS  Google Scholar 

  2. Stonik VA, Kalinin VI, Avilov SA (1999) Toxins from sea cucumbers (holothuroids): chemical structures, properties, toxonomic distribution, biosynthesis and evolution. J Nat Toxins 8:235–248

    CAS  Google Scholar 

  3. Kalinin VI, Aminin DL, Avilov SA, Silchenko AS, Stonik VA (2008) Triterpene glycosides from sea cucucmbers (Holothurioidae, Echinodermata), biological activities and functions. In: Atta-ur-Rahman (ed) Studies in natural product chemistry (bioactive natural products). Elsevier, The Netherlands, pp 135–196

    Google Scholar 

  4. Janakiram NB, Mohammed A, Zhang Y, Choi CI, Woodward C, Collin P, Steele VE, Rao CV (2010) Chemo-preventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth. Cancer Prev Res 3:82–91

    Article  CAS  Google Scholar 

  5. Girard M, Belanger J, ApSimon JW, Garneau FX, Harvey C, Brisson JR (1990) Frondoside A, novel triterpene glycoside from the holothurian Cucumaria frondosa. Can J Chem 68:11–18

    Article  CAS  Google Scholar 

  6. Avilov SA, Stonik VA, Kalinovsky AI (1990) Structures of four new triterpene glycosides from the sea cucumber Cucumaria japonica. Khim Prirodn Soedin 6:787–792

    Google Scholar 

  7. Drozdova OA, Avilov SA, Kalinovsky AI, Stonik VA, Milgrom YuM, Rashkes YaW (1993) Trisulfated glycosides from the sea cucumber Cucumaria japonica. Khim Prirodn Soedin 3:369–374

    Google Scholar 

  8. Drozdova OA, Avilov SA, Kalinin VI, Kalinovsky AI, Stonik VA, Rugiera R, Jimenez C (1997) Cytotoxic triterpene glycosides from Far-Eastern sea cucumber belonging to the genus Cucumaria. Liebigs Ann Chem 11:2351–2356

    Article  Google Scholar 

  9. Tong Y, Zhang X, Tian F, Yi Y, Xu Q, Li L, Tong L, Lin L, Ding J (2005) Philinopside A, a novel marine derived compound possessing dual anti-angiogenetic and anti-tumor effects. Int J Cancer 114:843–853

    Article  CAS  Google Scholar 

  10. Tian F, Zhang X, Tong Y, Yi Y, Zhang S, Li L, Sun P, Lin L, Ding J (2005) PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenetic and anti-tumor activities in vitro and in vivo. Cancer Biol Ther 4:874–882

    Article  CAS  Google Scholar 

  11. Li X, Roginsky AB, Ding XZ, Woodward C, Collin P, Newman RA (2008) Review of the apoptosis pathways in pancreatic cancer and the anti-apoptotic effects of the novel sea cucumber compound, Frondoside A novel sea cucumber compound, frondoside A. Ann N Y Acad Sci 1138:181–198

    Article  CAS  Google Scholar 

  12. Aminin DL, Chaykina EL, Agafonova IG, Avilov SA, Kalinin VI, Stonik VA (2010) Anti-tumor activity of the immunomodulatory lead Cumaside. Int Immunopharm 10:648–654

    Article  CAS  Google Scholar 

  13. Jin JO, Shastina VV, Shin SW, Xu Q, Park JI, Rasskazov VA, kwak JY (2009) Differential effects of triterpene glycosides, frondoside A and cucumarioside A2-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells. FEBS Lett 583:697–702

    Article  CAS  Google Scholar 

  14. Roginsky AB, Ding X-Z, Woodward C, Ujiki MB, Singh B, Bell RH Jr, Collin P, Adrian TE (2010) Anti-pancreatic cancer effects of a polar extract from the edible sea cucumber, Cucumaria frondosa. Pancreas 39:646–652

    Article  Google Scholar 

  15. Stonik VA, Elyakov GB (1998) Secondary metabolites from echinodens as chemo-taxonomic markers. Bioorg Marine Chem 2:43–88

    Article  Google Scholar 

  16. Kalinin VI, Levin VS, Stonik VA (1994) The chemical morphology: triterpene glycosides of sea cucumbers (Holothurioidea, Echinodermata). Dalnauka, Vladivostok, p 284

    Google Scholar 

  17. Kalinin VI, Silchenko AS, Avilov SA, Stonik VA, Smirnov AV (2005) Sea cucumbers triterpene glycosides, the recent progress in structural elucidation and chemotaxonomy. Phytochem Rev 4:221–236

    Article  CAS  Google Scholar 

  18. Avilov SA, Silchenko AS, Antonov AS, Kalinin VI, Kalinovsky AI, Smirnov AV, Dmitrenok PS, Evtushenko EV, Fedorov SN, Savina AS, Shubina LK, Stonik VA (2008) Synaptosides A and A1, two triterpene glycosides from the sea cucumber Synapta maculata containing 3-O-methylglucuronic acid and their cytotoxic activity against tumor cells. J Nat Prod 71:525–531

    Article  CAS  Google Scholar 

  19. Kalinin VI, Volkova OV, Likhatskaya GN, Prokofieva NG, Agafonova IG, Anisimov MM, Kalinovsky AI, Avilov SA, Stonik VA (1992) Hemolytic activity of triterpene glycosides from Cucumariidae family holothurians and evolution of this group of toxins. J Nat Toxins 1:17–30

    CAS  Google Scholar 

  20. Kalinin VI, Prokofieva NG, Likhatskaya GN, Schentsova EB, Agafonova IG, Avilov SA, Drozdova OA (1996) Hemolytic activities of triterpene glycosides from holothurian order Dendrochirota: some trends in the evolution of this group of toxins. Toxicon 34:475–483

    Article  CAS  Google Scholar 

  21. Anisimov MM (1987) Triterpene glycosides and structure-functional properties of biomembranes. Biologicheskie Nauki 10:49–63

    Google Scholar 

  22. Verbist JE (1993) Pharmacological effects of compounds from echinoderms. In: Jangoux M, Lawrence JM (eds) Echinoderm studies, vol 4. Balkema, Rotterdam, pp 111–186

    Google Scholar 

  23. Pislyagin EA, Gladkikh RV, Kapustina II, Kim NY, Shevchenko VP, Nagaev IY, Avilov SA, Aminin DL (2012) Interaction of holothurian triterpene glycoside with biomembranes of mouse immune cells. Int Immunopharmacol 14:1–8

    Article  CAS  Google Scholar 

  24. Mimaki Y, Yokosuka A, Kuroda M, Sashida Y (2001) Cytotoxic activities and structure–cytotoxic relationships of steroidal saponins. Biol Pharm Bull 24:1286–1289

    Article  CAS  Google Scholar 

  25. Aminin DL, Pinegin BV, Pichugina LV, Zaporozhets TS, Agafonova IG, Boguslavski VM, Silchenko AS, Avilov SA, Stonik VA (2006) Immunomodulatory properties of Cumaside. Int Immunopharmacol 6:1070–1082

    Article  CAS  Google Scholar 

  26. Miamoto T, Togawa K, Higuchi R, Komori T, Sasaki T (1990) Constituents of Holothurioidea II. Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber Cucumaria echinara. Liebigs Ann Chem 1990:453–460

    Google Scholar 

  27. Aminin DL, Agafonova IG, Berdyshev EV, Isachenko EG, Avilov SA, Stonik VA (2001) Immunomodulatory properties of cucumariosides from the edible Far-Eastern holothurian Cucumaria japonica. J Med Food 4:127–135

    Article  CAS  Google Scholar 

  28. Agafonova IG, Aminin DL, Avilov SA, Stonik VA (2003) Influence of cucumariosides upon intra-cellular [Ca2 +]i and lysosomal activity of macrophages. J Agric Food Chem 51:6982–6986

    Article  CAS  Google Scholar 

  29. Polikarpova SI, Volkova ON, Sedov AM, Stonik VA, Likhoded VG (1990) Cytogenetic study of the mutagenicity of cucumarioside. Genetika 26:1682–1685

    CAS  Google Scholar 

  30. Fedorov SN, Shubina LK, Kapustina II, Avilov SA, Kwak J-Y, Park J-I, Jin J-O, Kwon J-X, Shastina VV, Stonik VA (21 December 2007) Means inducing apoptosis in human leukemia cells. Patent of the Russian Federation No. 2360692, Bull Izobr No 19, 10 July 2009, Appl No 2007148013/15

    Google Scholar 

  31. Silchenko AS, Avilov SA, Kalinin VI, Kalinovsky AI, Dmitrenok PS, Fedorov SN, Stepanov VG, Dong Z, Stonik VA (2008) Constituents of the sea cucumber Cucumaria okhotensis. Structures of okhotosides B1–B3 and cytotoxic activities of some glycosides from this species. J Nat Prod 71:351–356

    Article  CAS  Google Scholar 

  32. Attoub S, Arafat K, Gélaude A, Al Sultan MA, Bracke M, Collin P, Takahashi T, Adrian TE, De Wever O (2013) Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis. PLoS One 8:e53087

    Article  CAS  Google Scholar 

  33. Silchenko AS, Kalinovsky AI, Avilov SA, Andryjaschenko PV, Dmitrenok PS, Yurchenko EA, Kalinin VI (2012) Structures and cytotoxic properties of cucumariosides H2, H3 and H4 from the sea cucumber Eupentacta fraudatrix. Nat Prod Res 26:1765–1774

    Article  CAS  Google Scholar 

  34. Silchenko AS, Kalinovsky AI, Avilov SA, Andryjaschenko PV, Dmitrenok PS, Menchinskaya ES, Aminin DL, Kalinin VI (2013) Structure of cucumarioside I2 from the sea cucumber Eupentacta fraudatrix (Djakonov et Baranova) and cytotoxic and immunostimulatory activities of this saponin and relative compounds. Nat Prod Res 27:1776–1783

    Article  CAS  Google Scholar 

  35. Zamzami N, Susin SA, Marchetti P, Hirsch T, Gómez-Monterrey I, Castedo M, Kroemer G (1996) Mitochondrial control of nuclear apoptosis. J Exp Med 183:1533–1544

    Article  CAS  Google Scholar 

  36. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prévost MC, Alzari PM, Kroemer G (1999) Mitochondrial release of caspase-2 and -9 during the apoptotic process. J Exp Med 189:381–394

    Article  CAS  Google Scholar 

  37. Green DR (2000) Apoptotic pathways: paper wraps stone blunts scissors. Cell 102:1–4

    Article  CAS  Google Scholar 

  38. Shi Y (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9:459–470

    Article  CAS  Google Scholar 

  39. Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567

    Article  CAS  Google Scholar 

  40. Leist M, Jäättelä M (2001) Four deaths and a funeral: from caspases to alter-native mechanisms. Nat Rev Mol Cell Biol 2:589–598

    Article  CAS  Google Scholar 

  41. Kroemer G, Martin SJ (2005) Caspase-independent cell death. Nat Med 1:725–730

    Article  Google Scholar 

  42. Ravagnan L, Roumier T, Kroemer G (2002) Mitochondria, the killer organelles and their weapons. J Cell Physiol 192:131–137

    Article  CAS  Google Scholar 

  43. Cregan SP, Dawson VL, Slack RS (2004) Role of AIF in caspase-dependent and caspase-independent cell death. Oncogene 23:2785–2796

    Article  CAS  Google Scholar 

  44. Al Marzouqi N, Iratni R, Nemmar A, Arafat K, Ahmed Al Sultan M, Yasin J, Collin P, Mester J, Adrian TE, Attoub S (2011) Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts. Eur J Pharmacol 668:25–34

    Article  CAS  Google Scholar 

  45. Ma X, Kundu N, Collin PD, Goloubeva O, Fulton AM (2011) Frondoside A inhibits breast cancer metastasis and antagonizes prostaglandin E receptors EP4 and EP2. Breast Cancer Res Treat 132:1001–1008

    Article  Google Scholar 

  46. Holt DM, Ma X, Kundu N, Collin PD, Fulton AM (2012) Modulation of host natural killer cell functions in breast cancer via prostaglandin E2 receptors EP2 and EP4. J Immunother 35:179–188

    Article  CAS  Google Scholar 

  47. Park SY, Kim YH, Kim Y, Lee SJ (2012) Frondoside A has an anti-invasive effect by inhibiting TPA-induced MMP-9 activation via NF-κB and AP-1 signaling in human breast cancer cells. Int J Oncol 41:933–940

    CAS  Google Scholar 

  48. Weng CJ, Chau CF, Hsieh YS, Yang SF, Yen GC (2008) Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-κB and AP-1. Carcinogenesis 29:147–156

    Article  CAS  Google Scholar 

  49. Aminin DL, Gorpenchenko TY, Bulgakov VP, Andryjashchenko PV, Avilov SA, Kalinin VI (2011) Triterpene glycoside cucumarioside A2-2 from sea cucumber stimulates mouse immune cell adhesion, spreading, and motility. J Med Food 14:594–600

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2012–0009583 and 2012–0009664).

Author information

Authors and Affiliations

  1. Immune-network Pioneer Research Center & Department of Biochemistry, School of Medicine, Dong-A University, 3-1, Dongdaesin-Dong, Seo-Gu, Busan 602-714, Korea

    Chang Gun Kim & Prof. Jong-Young Kwak

Authors
  1. Chang Gun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prof. Jong-Young Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Marine-Bio Convergence Science, Pukyong National University, Busan, Korea, Republic of (South Korea)

    Se-Kwon Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kim, C., Kwak, JY. (2015). Anti-cancer Effects of Triterpene Glycosides, Frondoside A and Cucumarioside A2-2 Isolated from Sea Cucumbers. In: Kim, SK. (eds) Handbook of Anticancer Drugs from Marine Origin. Springer, Cham. https://doi.org/10.1007/978-3-319-07145-9_31

Download citation

Publish with us

Policies and ethics

Search

Navigation