Molluscs pp 363-379 | Cite as

Kahalalide F and ES285: Potent Anticancer Agents from Marine Molluscs

  • G. Faircloth
  • Maria del Carmen Cuevas Marchante
Chapter
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 43)

Abstract

The marine environment is proving to be a very rich source of unique compounds with significant activities against cancer of several types. Finding the sources of these new chemical entities has made it necessary for marine and medical scientists to find enterprising ways to collaborate in order to sample the great variety of intertidal, shallow and deep-water sea life. Recently these efforts resulted in a first generation of drugs from the sea undergoing clinical trials. These include PharmaMar compounds: Yondelis, Aplidin, kahalalide F, ES285 and Zalypsis. Two of these compounds, kahalalide F and ES285, have been isolated from the Indopacific mollusc Elysia rufescens and the North Atlantic mollusc Spisula polynyma, respectively.

Keywords

Maximum Tolerate Dose Marine Mollusc Potent Anticancer Agent Solid Tumour Cell Line Alpha Mannosidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Becerro MA, Paul VJ, Goetz G, Scheuer PJ (2001) Chemical defences of the sacoglossan mollusk Elysia rufescens and its host alga Briopsis sp. J Chem Ecol 27:2287–2299PubMedCrossRefGoogle Scholar
  2. Brown AP, Morrissey RL, Faircloth GT, Levine BS (2002) Preclinical toxicity of Kahalalide F, a new anticancer agent: single and multiple dosing regimens in the rat. Cancer Chemother Pharmacol 50:333–340PubMedCrossRefGoogle Scholar
  3. Ciruelos C, Trigo J, Pardo J, Paz-Ares L, Estaun N, Cuadra C, Domínguez M, Marín A, Jimeno JM, Izquierdo M (2002) A phase I clinical and pharmacokinetic study with Kahalalide F in patients with advanced solid tumours with a continuous weekly 1-hour iv infusion schedule. Eur J Cancer 38:33CrossRefGoogle Scholar
  4. Córdoba S, Zapata I, Romero J, de la Torre A, López-Martin JA, Vargas JA, Sánchez-Prieto R, Corbacho C, Regueiro CA, Magallón R (2003) In vitro chemosensitivity, cell cycle redistribution and apoptosis induction by Kahalalide F, a new marine compound in a panel of human tumoural cells. Eur J Cancer Suppl 1:S173CrossRefGoogle Scholar
  5. Cuadros R, Montejo de Garcini E, Wandosell F, Faircloth GT, Fernández-Sousa JM, Avila J (2000) The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett 152:23–29PubMedCrossRefGoogle Scholar
  6. Gajate C, An F, Nieto-Miguel T, Mollinedo F (2005) Induction of apoptosis by the novel marine-derived antitumour agent ES-285 (spisulosine): cell cycle arrest, and mitochondrial and caspase involvement (in press)Google Scholar
  7. <AQ. Please update Gajate et al. (2005).>Google Scholar
  8. García-Rocha M, Bonay P, Avila J (1996) The antitumoural compound Kahalalide F acts on cell lysosomes. Cancer Lett 99:43–50PubMedCrossRefGoogle Scholar
  9. Gómez SG, Bueren JA, Faircloth GT, Jimeno J, Albella B (2003) In vitro toxicity of three new antitumoural drugs (trabectedin, aplidin and kahalalide F) on hematopoietic progenitors and stem cells. Exp Hematol 31:1104–1111PubMedGoogle Scholar
  10. Green BJ, Li W, Manhart JR, Fox TC, Summer EJ, Kennedy RA, Pierce SK, Rumpho ME (2000) Mollusc–algal chloroplast endosymbiosis. Photosynthesis, thylakoid protein maintenance, and chloroplast gene expression continue for many months in the absence of the algal nucleus. Plant Physiol 124:331–342PubMedCrossRefGoogle Scholar
  11. Hamann MT, Scheuer PJ (1993) Kahalalide F: a bioactive depsipeptide from the sacoglossan mollusk Elysia rufescens and the green alga Bryopsis sp. J Am Chem Soc 115:5825–5826CrossRefGoogle Scholar
  12. Hamann MT, Otto CS, Scheuer PJ, Dunbar DC (1996) Kahalalides, bioactive depsipeptides from the sacoblassan mollusk Elysia rufescens and the green alga Bryopsis sp. J Org Chem 61:6594–6600PubMedCrossRefGoogle Scholar
  13. Janmaat ML, Kruyt FAE, Jimeno J, Rodríguez JA, Giaccone G (2004) Kahalalide F induces caspase-independent cytotoxicity that correlates with HER2 and/or HER3 expression levels and is accompanied by down-regulation of AKT signaling. Proc AACR 95:5328Google Scholar
  14. Lacal JC, Rodríguez-González A, Alvarez-Miranda M (2004) Study of the mechanism of action of ES285. PharmaMar, MadridGoogle Scholar
  15. López-Maciá A, Jiménez JC, Royo M, Giralt E, Albericio F (2001) Synthesis and structural determination of Kahalalide F. J Am Chem Soc 123:11398–11401PubMedCrossRefGoogle Scholar
  16. Nuijen B, Bouma M, Talsma H, Manada C, Jimeno JM, López-Lazaro L, Bult A, Beijnen JH (2001) Development of a lyophilized, parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent Kahalalide F. Drug Dev Ind Pharm 27:767–780PubMedCrossRefGoogle Scholar
  17. Rinehart KL, Fregeau NL, Warwick RA (1998) US patent 6107520cGoogle Scholar
  18. Salcedo M (2005) The marine antitumour compound ES 285 activates EGD receptors and PKC, and in parallel triggers an atypical cell death pathway (in press)Google Scholar
  19. Salcedo M, Cuevas C, Sánchez-Puelles JM, Otero G, Sousa JM, Avila J, Wandosell F (2003) Proc Am Assoc Cancer Res 44:3649Google Scholar
  20. Schellens JH, Rademaker JL, Horenblas S, Meinhardt W, Stukvis E, de Reijke TM, Jimeno JM, López-Lazaro L, López-Martín JA, Beijnen JH (2002) Phase I and pharmacokinetic study of Kahalalide F in patients with advanced androgen refractory prostate cancer. Proc ASCO 38:451Google Scholar
  21. Sewell JM, Langdon SP, Smyth JF, Jodrell I, Guichard S (2004) Kahalalide F appears to promote necrotic cell death in hepatoma cell lines. Proc AACR 95:1509Google Scholar
  22. Suárez J, Gonzalez L, Cuadrado A, Berciano M, Lafarga M, Muñoz A (2003) Kahalalide F, a new marine-derived compound induces oncosis in human prostate and breast cancer cells. Mol Cancer Ther 2:863–872PubMedGoogle Scholar
  23. Tartakoff AM (1983) Perturbations of vesicular traffic with the carboxylic ionophore monensin. Cell 32:1026–1028PubMedCrossRefGoogle Scholar
  24. Wosikowski K, Schuurhuis D, Johnson K (1997) Identification of Epidermal growth factor receptor and c-ErbB2 pathway inhibitors by correlation with gene expression patterns. J Nat Cancer Inst 89:1505–1515PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • G. Faircloth
  • Maria del Carmen Cuevas Marchante
    • 1
  1. 1.PharmaMar SAColmenar Vieja, MadridSpain

Personalised recommendations