Skip to main content
Log in

Antitumor potential of natural products from Mediterranean ascidians

  • Published:
Phytochemistry Reviews Aims and scope Submit manuscript

Abstract

Ascidians, invertebrates belonging to the subphylum Urochordata (Tunicata), are renowned for their great chemical diversity, and during the last 25 years, they have been shown to produce an array of cytotoxic molecules. Among the first six marine-derived compounds that have reached clinical trials as antitumor agents, three are derived from ascidians, as evidence of the high potential of these organisms as a new source of antitumor compounds. Reported in this communication are some recent results on the chemistry of Mediterranean ascidians; a number of new molecules with different structural features but all endowed with antiproliferative or cytotoxic activity are discussed. These results strongly evidence the highly significant role that Mediterranean ascidians natural products could play in anticancer drug discovery and development process.

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

Similar content being viewed by others

References

  • Aiello A, Fattorusso E, Menna M, Carnucccio R, D’Acquisto F (1997a) Novel antiproliferative alkyl sulfates from the Mediterranean tunicate Ascidia mentula. Tetrahedron 53:5877–5882

    Article  CAS  Google Scholar 

  • Aiello A, Fattorusso E, Menna M, Carnucccio R, Iuvone T (1997b) A new antiproliferative sulfated alkene from the Mediterranean tunicate Microcosmus vulgaris. Tetrahedron 53:11489–11492

    Article  CAS  Google Scholar 

  • Aiello A, Fattorusso E, Menna M (1999) Steroids from sponges: recent reports. Steroids 64:687–714

    Article  PubMed  CAS  Google Scholar 

  • Aiello A, Carbonelli S, Esposito G, Fattorusso E, Iuvone T, Menna M (2000) Novel bioactive sulfated alkene and alkanes from the Mediterranean ascidian Halocynthia papillosa. J Nat Prod 63:1590–1592

    Article  PubMed  CAS  Google Scholar 

  • Aiello A, Carbonelli S, Esposito G, Fattorusso E, Iuvone T, Menna M (2001a) Turbinamide, a new selective cytotoxic agent from the Mediterranean tunicate Sidnyum turbinatum. Org Lett 3(19):2941–2944

    Article  PubMed  CAS  Google Scholar 

  • Aiello A, Carbonelli S, Fattorusso E, Iuvone T, Menna M (2001b) New bioactive sulfated metabolites from the Mediterranean tunicate Sidnyum turbinatum. J Nat Prod 64:219–221

    Article  PubMed  CAS  Google Scholar 

  • Aiello A, Fattorusso E, Luciano P, Menna M, Esposito G, Iuvone T, Pala D (2003) Conicaquinones A and B, two novel cytotoxic terpene quinones from the Mediterranean ascidian Aplidium conicum. Eur J Org Chem 2003(5):898–900

    Article  Google Scholar 

  • Aiello A, Fattorusso E, Luciano P, Macho A, Menna M, Muñoz E (2005a) Antitumor effects of two novel naturally occurring terpene quinones isolated from the Mediterranean ascidian Aplidium conicum. J Med Lett 48:3410–3416

    CAS  Google Scholar 

  • Aiello A, Fattorusso E, Luciano P, Mangoni A, Menna M (2005b) Isolation and structure determination of Aplidinones A-C from the Mediterranean ascidian Aplidium conicum: a successful regiochemistry assignment by quantum mechanical 13C NMR chemical shift calculations. Eur J Org Chem 2005(23):5024–5030

    Article  CAS  Google Scholar 

  • Aiello A, Fattorusso E, Giordano A, Menna M, Navarrete C, Muñoz E (2007) Clavaminols A–F, novel cytotoxic 2-amino-3-alkanols from the ascidian Clavelina phlegraea. Bioorg Med Chem 15(8):2920–2926

    Article  PubMed  CAS  Google Scholar 

  • Aiello A, Fattorusso E, Giordano A, Menna M, Navarrete C, Muñoz E (2009) Clavaminols G-N, six new marine sphingoids from the Mediterranean ascidian Clavelina phlegraea. Tetrahedron. doi:10.1016/j.tet.2009.03.056

  • Amador ML, Jimeno J, Paz-Ares L, Cortes-Funes H, Hidalgo M (2003) Progress in the development and acquisition of anticancer agents from marine sources. Ann Oncol 14:1607–1615

    Article  PubMed  CAS  Google Scholar 

  • Bergmann W, Feeney R (1951) Contribution to the study of marine products. XXXII. The nucleosides of sponges. J Org Chem 16:981–987

    Article  CAS  Google Scholar 

  • Blunt JW, Copp BR, Hu W et al (2008) Marine natural products. Nat Prod Rep 25:35–94

    Article  PubMed  CAS  Google Scholar 

  • Bonetta L (2001) Anticancer squirt. Nat Med 7:891

    Article  PubMed  CAS  Google Scholar 

  • Crispino A, De Giulio A, De Rosa S, De Stefano S, Milone A, Zavodnik N (1994) A sulfated normonoterpenoid from the Ascidian Polycitor adriaticus. J Nat Prod 57:1575–1577

    Article  CAS  Google Scholar 

  • Cruz-Monserrate Z, Vervoort HC, Bai R, Newman DJ, Howell SB, Los G, Mullaney JT, Williams MD, Pettit GR, Fenical W, Hamel E (2003) Diazonamide A and a synthetic structural analog: disruptive effects on mitosis and cellular microtubules and analysis of their interactions with tubulin. Mol Pharmacol 63:1273–1280

    Article  PubMed  CAS  Google Scholar 

  • Cuadros R, Montejo de Garcini E, Wandosell F, Faircloth G, Fernandez-Sousa J, Avila J (2000) The marine compound spisulosine, an inhibitor of cell proliferation promotes the disassembly of actin stress fibers. Cancer Lett 152:23–29

    Article  PubMed  CAS  Google Scholar 

  • De Rosa S, Milone A, Crispino A, Jaklin A, De Giulio A (1997) Absolute configuration of 2, 6-dimethylheptyl sulfate and its distribution in Ascidiacea. J Nat Prod 60:462–463

    Article  Google Scholar 

  • de Tinguy-Moreaud E, Pourquier P, Montaudon D, Robert J (1994) Relationships between DNA damage and growth inhibition induced by topoisomerase II-interfering drugs in doxorubicin-sensitive and -resistant rat glioblastoma cells. Anticancer Res 14:99–103

    PubMed  Google Scholar 

  • Edler MC, Fernandez AM, Lassota P, Ireland CM, Barrows LR (2002) Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10. Biochem Pharm 63(4):707–715

    Article  PubMed  CAS  Google Scholar 

  • Esposito G, Aiello A, Carbonelli S, Menna M, Fattorusso E, Iuvone T (2002) Mechanism of cytotoxicity of turbinamide in vitro. Anticancer Res 22:2827–2832

    PubMed  CAS  Google Scholar 

  • Faivre S, Chièze S, Delbaldo C, Ady-vago N, Guzman C, Lopez-Lazaro L, Lozahic S, Jimeno J, Pico F, Armand JP, Lopez Martin JA, Raymond E (2005) Phase I and pharmacokinetic study of Aplidine, a new marine cyclodepsipeptide in patients with advanced malignancies. J Clin Oncol 23:7871–7880

    Article  PubMed  CAS  Google Scholar 

  • Fenical W (1976) Geranyl hydroquinone, a cancer-protective agent from the tunicate Aplidium species. Food-Drugs Sea Proc 4:388–394

    Google Scholar 

  • Findlay JA, He Z, Calhoun LA (1990) Forbesin: a novel sulfated glycolipid from the starfish Asterias forbesi. J Nat Prod 53:1015–1018

    Article  CAS  Google Scholar 

  • Findlay JA, Yayli N, Calhoun LA (1991) Novel sulfated hydrocarbons from the sea cucumber Cucumaria frondosa. J Nat Prod 54:302–304

    Article  CAS  Google Scholar 

  • Fujita M, Nakao Y, Matsunaga S, Nishikawa T, Fusetani N (2002) Sodium 1-(12-hydroxy) octadecanyl sulfate, an MMP2 inhibitor, isolated from a tunicate of the family Polyclinidae. J Nat Prod 65:1936–1938

    Article  PubMed  CAS  Google Scholar 

  • Garrido L, Zubia E, Ortega MJ, Salvà J (2002) New meroterpenoids from the ascidian Aplidium conicum. J Nat Prod 65:1328–1331

    Article  PubMed  CAS  Google Scholar 

  • Inbaraj JJ, Gandhisan R, Murugesan R (1999) Cytotoxicity and superoxide anion generation by some naturally occurring quinones. Free Radic Biol Med 26:1072–1078

    Article  CAS  Google Scholar 

  • Ireland CM, Fernandez A (1998) Cyclic peptide antitumor agent from an ascidian. PCT Int. Appl. 02.04.1998

  • Jimeno J, García-Grávalos D, Ávila J, Smith B, Grant W, Faircloth GT (1999) ES-285, a marine natural product with activity against solid tumors. AACR-NCI-EORTC international conference on molecular targets and cancer therapeutics. Washington DC, 16–19 Nov 1999, Abstract no. 314

  • Kijjoa A, Sawangwong P (2004) Drugs and cosmetics from the sea. Mar Drugs 2004:73–82

    Article  Google Scholar 

  • Kurata K, Taniguchi K, Suzuki M (1996) Cyclozonarone, a sesquiterpene-substituted benzoquinone derivative from the brown alga Dyctiopteris undulate. Phytochemistry 47:749–752

    Article  Google Scholar 

  • Lawen A, Martinus RD, Mcmullen GL, Nagley P, Vaillant F, Wolvetang EJ, Linnane AW (1994) The universality of bioenergetic disease: the role of mitochondrial mutation and the putative inter-relationship between mitochondria and plasma membrane NADH oxidoreductase. Mol Aspects Med 15(Suppl):13–27

    Article  Google Scholar 

  • Lievens SC, Molinski TF (2005) Sagittamides A and B. Polyacetoxy long-chain acyl amino acids from a Didemnid Ascidian. Org Lett 7(11):2281–2284

    Article  PubMed  CAS  Google Scholar 

  • Lindquist N, Fenical W, Van Duyne GD, Clardy J (1991) Isolation and structure determination of diazonamides A and B, unusual cytotoxic metabolites from the marine ascidian Diazona chinensis. J Am Chem Soc 113(6):2303–2304

    Article  CAS  Google Scholar 

  • Ly JD, Lawen A (2003) Transplasma membrane electron transport: enzymes involved and biological function. Redox Rep 8:3–21

    Article  PubMed  CAS  Google Scholar 

  • Manzanares I, Cuevas C, Garcia-Nieto R, Marco E, Gago F (2001) Advances in the chemistry and pharmacology of ecteinascidins, a promising new class of anticancer agents. Curr Med Chem-Anti-Cancer Agents 1:257–276

    Article  CAS  Google Scholar 

  • Minale L, Riccio R, Sodano G (1974) Avarol, a novel sesquiterpenoid hydroquinone with a rearranged drimane skeleton from the sponge Dysidea avara. Tetrahedron Lett 38:3401–3404

    Article  Google Scholar 

  • Nakao Y, Matsunaga S, Fusetani N (1993) Toxadocial A: a novel thrombin inhibitor from the marine sponge toxadocia cylindrical. Tetrahedron Lett 34(9):1511–1514

    Article  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2004a) Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Curr Med Chem 11:1693–1713

    PubMed  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2004b) Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 67(8):1216–1238

    Article  PubMed  CAS  Google Scholar 

  • Riccio R, Iorizzi M, Minale L (1987) Recent advances in the chemistry of Echinoderms. In: Hostettmann K, Lea PJ (eds) Biologically active natural products. Clarendon Press, Oxford

    Google Scholar 

  • Rinehart LK (2000) Antitumor compounds from tunicates. Med Res Rev 20(1):1–27

    Article  PubMed  CAS  Google Scholar 

  • Rinehart LK, Gloer JB, Carter Cook J, Mizsak S, Scahill TA (1981) Structure of the didemnins, antiviral and cytotoxic depsipeptides from a Caribbean tunicate. J Am Chem Soc 103:1857–1859

    Article  CAS  Google Scholar 

  • Rinehart K, Holt TG, Fregeau NL, Stroh JG, Kiefer PA, Sun F, Li LH, Martin DG (1990) Ecyeinascidin 729, 743, 759A, and 770: potent antutumor agents from the Caribbean tunicate Ecteinascidia turbinata. J Org Chem 55:4512–4515

    Article  CAS  Google Scholar 

  • Roccatagliata AJ, Maier MS, Seldes AM, Zea S, Duque C (1997) A new sulfated alkene from the ophiuroid Ophiocoma echinata. J Nat Prod 60:285–286

    Article  CAS  Google Scholar 

  • Sánchez AM, Malagarie-Cazenave S, Olea N, Vara D, Cuevas C, Díaz-Laviada I (2008) Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCζ activation. Eur J Pharmacol 584:237–245

    Article  PubMed  CAS  Google Scholar 

  • Smith MT (1985) Quinones as mutagens, carcinogens and anticancer agents: introduction and overview. J Toxicol Environ Health 16:665–672

    Article  PubMed  CAS  Google Scholar 

  • Takebayashi Y, Pourquier P, Zimonjic DB, Nakayama K, Emmert S, Ueda T, Urasaki Y, Kanzaki A, Akiyama S, Popescu N, Kraemer KH, Pommier Y (2001) Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med 7:961–966

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto S, Kato H, Hirota H, Fusetani N (1994) Antibacterial and antifungal sulfated alkane and alkenes from the Hepatopancreas of the ascidian Halocynthia Roretzi. J Nat Prod 57:1606–1609

    Article  PubMed  CAS  Google Scholar 

  • Urdiales JL, Morata P, Nunez de Castro I, Sanchez-Jimenez F (1996) Antiproliferative effect of dehydrodidemin B (DDB), a depsipeptide isolated from Mediterraneam tunicates. Cancer Lett 102:31–37

    Article  PubMed  CAS  Google Scholar 

  • Wright AE, Forleo DA, Gunawardana GP, Gunasekera SP, Koehn FE, McConnell OJ (1990) Antitumor tetrahydroisoquinoline alkaloids from the colonial ascidian Ecteinascidia turbinata. J Org Chem 55:4508–4512

    Article  CAS  Google Scholar 

  • Zubìa E, Ortega M, Salvà J (2005) Natural products chemistry in marine ascidians of the genus Aplidium. Mini-Rev Org Chem 2:546–564

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marialuisa Menna.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Menna, M. Antitumor potential of natural products from Mediterranean ascidians. Phytochem Rev 8, 461–472 (2009). https://doi.org/10.1007/s11101-009-9131-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11101-009-9131-y

Keywords

Navigation