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Molluscs pp 215-239 | Cite as

Bioactive Molecules from Sea Hares

Chapter
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 43)

Abstract

Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and “shell-less” snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the “Aplysianin A family,” although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an à-amino group of the substrate with molecular oxygen and liberates hydrogen peroxide, with a sequence similar to other known LAAOs, including snake venom. Possible antibacterial activity and cytotoxic activity mechanisms of these proteins are also discussed.

Keywords

Bioactive Molecule Acute Liver Damage Albumen Gland Chemical Defense Mechanism Giant African Snail 
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.
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References

  1. Ahn MY, Lee BM, Kim YS (1997) Characterization and cytotoxicity of L-amino acid oxidase from the venom of king cobra (Ophiophagus hannah). Int J Biochem Cell Biol 29:911–919PubMedCrossRefGoogle Scholar
  2. 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 14:1607–1615PubMedCrossRefGoogle Scholar
  3. Avila C (1995) Natural products of opisthobranch molluscs: a biological review. Oceanogr Mar Biol Annu Rev 33:487–559Google Scholar
  4. Bai R, Verdier-Pinard P, Gangwar S, Stessman CC, McClure KJ, Sausville EA, Pettit GR, Bates RB, Hamel E (2001) Dolastatin 11, a marine depsipeptide, arrests cells at cytokinesis and induces hyperpolymerization of purified actin. Mol Pharmacol 59:462–469PubMedGoogle Scholar
  5. Bai R, Covell DG, Liu C, Ghosh AK, Hamel E (2002) (-)-Doliculide, a new macrocyclic depsipeptide enhancer of actin assembly. J Biol Chem 277:32165–32171PubMedCrossRefGoogle Scholar
  6. Beeman (1977) Gastropoda:Opisthobranchia. In: Giese AC, Pearse JS (eds) Reproduction of marine invertebrates. Vol IV. Molluscs: gastropods and cephalopods. Academic, New York, pp 115–179Google Scholar
  7. Bonnet MS, Basson PW (2002) The toxicology of Amanita phalloides. Homeopathy 91:249–254PubMedCrossRefGoogle Scholar
  8. Brandi G, Fiorani M, Pierotti C, Albano A, Cattabeni F, Cantoni O (1989) Morphological changes in Escherichia coli cells exposed to low or high concentrations of hydrogen peroxide. Microbiol Immunol 33:991–1000PubMedGoogle Scholar
  9. Bubb MR, Senderowicz AM, Sausville EA, Duncan KL, Korn ED (1994) Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. J Biol Chem 269:14869–14871PubMedGoogle Scholar
  10. Bubb MR, Spector I, Bershadsky AD, Korn ED (1995) Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments. J Biol Chem 270:3463–3466PubMedCrossRefGoogle Scholar
  11. Butzke D, Machuy N, Thiede B, Hurwitz R, Goedert S, Rudel T (2004) Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways. Cell Death Differ 11:608–617PubMedGoogle Scholar
  12. Butzke D, Hurwitz R, Thiede B, Goedert S, Rudel T (2005) Cloning and biochemical characterization of APIT, a new L-amino acid oxidase from Aplysia punctata. Toxicon 46:479 489Google Scholar
  13. Chu CC, Paul WE (1997) Fig1, an interleukin 4-induced mouse B cell gene isolated by cDNA representational difference analysis. Proc Natl Acad Sci USA 94:2507–2512PubMedCrossRefGoogle Scholar
  14. Cimino G, Fontana A, Gavagnin M (1999) Marine opisthobranch molluscs: chemistry and ecology in sacoglossans and dorids. Curr Org Chem 3:327–372Google Scholar
  15. Cimino G, Ciavatta ML, Fontana A, Gavagnin M (2001) Metabolites of marine opisthobranchs: chemistry and biological activity. In: Tingali C (ed) Bioactive compounds from natural sources. Taylor and Francis, London, pp 577–637Google Scholar
  16. Cummins SF, Nichols AE, Amare A, Hummon AB, Sweedler JV, Nagle GT (2004a) Characterization of Aplysia enticin and temptin, two novel water-borne protein pheromones that act in concert with attractin to stimulate mate attraction. J Biol Chem 279:25614–25622PubMedCrossRefGoogle Scholar
  17. Cummins SF, Nichols AE, Rajarathnam K, Nagle GT (2004b) A conserved heptapeptide sequence in the waterborne attractin pheromone stimulates mate attraction in Aplysia. Peptides 25:185–189PubMedCrossRefGoogle Scholar
  18. Du XY, Clemetson KJ (2002) Snake venom L-amino acid oxidases. Toxicon 40:659–665PubMedCrossRefGoogle Scholar
  19. Ehara T, Kitajima S, Kanzawa N, Tamiya T, Tsuchiya T (2002) Antimicrobial action of achacin is mediated by L-amino acid oxidase activity. FEBS Lett 531:509–512PubMedCrossRefGoogle Scholar
  20. Furukawa K, Sakai K, Watanabe S, Maruyama K, Murakami M, Yamaguchi K, Ohizumi Y (1993) Goniodomin A induces modulation of actomyosin ATPase activity mediated through conformational change of actin. J Biol Chem 268:26026–26031PubMedGoogle Scholar
  21. Gilboa-Garber N, Susswein AJ, Mizrahi L, Avichezer D (1985) Purification and characterization of the gonad lectin of Aplysia depilans. FEBS Lett 181:267–270PubMedCrossRefGoogle Scholar
  22. Halstead BW, Courville DA (1965) Poisonous sea hares. In: USGPO (ed) Poisonous and venomous marine animals of the world, Vol 1. United States Government Printing Office, Washington, DC, pp 709–715Google Scholar
  23. Hino K, Mitsui Y, Hirano Y (1994) Four cases of acute liver damage following the ingestion of a sea hare egg. J Gastroenterol 29:679PubMedCrossRefGoogle Scholar
  24. Hyslop PA, Hinshaw DB, Scraufstatter IU, Cochrane CG, Kunz S, Vosbeck K (1995) Hydrogen peroxide as a potent bacteriostatic antibiotic: implications for host defense. Free Radic Biol Med 19:31–37PubMedCrossRefGoogle Scholar
  25. Iijima R, Kisugi J, Yamazaki M (2003a) L-Amino acid oxidase activity of an antineoplastic factor of a marine mollusk and its relationship to cytotoxicity. Dev Comp Immunol 27:505–512PubMedCrossRefGoogle Scholar
  26. Iijima R, Kisugi J, Yamazaki M (2003b) A novel antimicrobial peptide from the sea hare Dolabella auricularia. Dev Comp Immunol 27:305–311PubMedCrossRefGoogle Scholar
  27. Iijima R, Takahashi H, Namme R, Ikegami S, Yamazaki M (2004) Novel biological function of sialic acid (N-acetylneuraminic acid) as a hydrogen peroxide scavenger. FEBS Lett 561:163–166PubMedCrossRefGoogle Scholar
  28. Ishiwata H, Nemoto T, Ojika M, Yamada K (1994) Isolation and structure of doliculide, a cytotoxic cyclodepsipeptide from Japanese sea hare Dolabella auricularia. J Org Chem 59:4712–4713CrossRefGoogle Scholar
  29. Jimbo M, Nakanishi F, Sakai R, Muramoto K, Kamiya H (2003) Characterization of L-amino acid oxidase and antimicrobial activity of aplysianin A, a sea hare-derived antitumor–antimicrobial protein. Fish Sci 69:1240–1246CrossRefGoogle Scholar
  30. Johnson P, Willows A (1999) Defensive sea hare (Gastropoda, Opisthobranchia, Anaspidea): multiple layers of protection from egg to adult. Mar Freshwater Behav Physiol 32:147–180CrossRefGoogle Scholar
  31. Jung SK, Mai A, Iwamoto M, Arizono N, Fujimoto D, Sakamaki K, Yonehara S (2000) Purification and cloning of an apoptosis-inducing protein derived from fish infected with Anisakis simplex, a causative nematode of human anisakiasis. J Immunol 165:1491–1497PubMedGoogle Scholar
  32. Kamiya H, Shimizu Y (1981) A natural agglutinin inhibitable by D-galacturonic acid in sea hare Aplysia eggs: characterization and purification. Bull Jpn Soc Fish 47:255–259CrossRefGoogle Scholar
  33. Kamiya H, Muramoto K, Ogata K (1984) Antibacterian activity in the egg mass of a sea hare. Experientia 40:947–949CrossRefGoogle Scholar
  34. Kamiya H, Muramoto K, Yamazaki M (1986) Aplysianin-A, an antibacterial and antineoplastic glycoprotein in the albumen gland of a sea hare, Aplysia kurodai. Experientia 42:1065–1067PubMedCrossRefGoogle Scholar
  35. Kamiya H, Muramoto K, Goto R, Yamazaki M (1988) Characterization of the antibacterial and antineoplastic glycoproteins in a sea hare Aplysia juliana. Nippon Suisan Gakkaishi 54:773–777CrossRefGoogle Scholar
  36. Kamiya H, Muramoto K, Goto R, Sakai M, Endo Y, Yamazaki M (1989) Purification and characterization of an antibacterial and antineoplastic protein secretion of a sea hare, Aplysia juliana. Toxicon 27:1269–1277PubMedCrossRefGoogle Scholar
  37. Kanzawa N, Shintani S, Ohta K, Kitajima S, Ehara T, Kobayashi H, Kizaki H, Tsuchiya T (2004) Achacin induces cell death in HeLa cells through two different mechanisms. Arch Biochem Biophys 422:103–109PubMedCrossRefGoogle Scholar
  38. Kigoshi H, Suenaga K, Takagi M, Akao A, Kanematsu K, Kamei N, Okugawa Y, Yamada K (2002) Cytotoxicity and actin-depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and its analogs. Tetrahedron 58:1075–1102CrossRefGoogle Scholar
  39. Kisugi J, Kamiya H, Yamazaki M (1987) Purification and characterization of aplysianin E, an antitumor factor from sea hare eggs. Cancer Res 47:5649–5653PubMedGoogle Scholar
  40. Kisugi J, Kamiya H, Yamazaki M (1989) Purification of dolabellanin-C an antineoplastic glycoprotein in the body fluid of a sea hare, Dolabella auricularia. Dev Comp Immunol 13:3–8PubMedCrossRefGoogle Scholar
  41. Klenchin VA, Allingham JS, King R, Tanaka J, Marriott G, Rayment I (2003) Trisoxazole macrolide toxins mimic the binding of actin-capping proteins to actin. Nat Struct Biol 10:1058–1063PubMedCrossRefGoogle Scholar
  42. Kobayashi M, Kanda F, Kamiya H (1991) Occurrence of pyropheophorbides a and b in the viscera of the sea hare Aplysia juliana. Nippon Suisan Gakkaishi 57:1983CrossRefGoogle Scholar
  43. Kobayashi M, Kawazoe K, Okamoto T, Sasaki T, Kitagawa I (1994) Marine natural products. XXXI. Structure–activity correlation of a potent cytotoxic dimeric macrolide swinholide A, from the Okinawan marine sponge Theonella swinhoei, and its isomers. Chem Pharm Bull 42:19–26PubMedGoogle Scholar
  44. Luesch H, Harrigan G, Goetz G, Horgen F (2002) The cyanobacterial origin of potent anticancer agents originally isolated from sea hares. Curr Med Chem 9:1791–1806PubMedGoogle Scholar
  45. Marquez BL, Watts KS, Yokochi A, Roberts MA, Verdier-Pinard P, Jimenez JI, Hamel E, Scheuer PJ, Gerwick WH (2002) Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J Nat Prod 65:866–871PubMedCrossRefGoogle Scholar
  46. Mason JM, Naidu MD, Barcia M, Porti D, Chavan SS, Chu CC (2004) IL-4-induced gene-1 is a leukocyte L-amino acid oxidase with an unusual acidic pH preference and lysosomal localization. J Immunol 173:4561–4567PubMedGoogle Scholar
  47. Melo VM, Duarte AB, Carvalho AF, Siebra EA, Vasconcelos IM (2000) Purification of a novel antibacterial and haemagglutinating protein from the purple gland of the sea hare, Aplysia dactylomela Rang, 1828. Toxicon 38:1415–1427PubMedCrossRefGoogle Scholar
  48. Millet AC, Ewbank JJ (2004) Immunity in Caenorhabditis elegans. Curr Opin Immunol 16:4–9PubMedCrossRefGoogle Scholar
  49. Müller WE, Zahn RK, Kurelec B, Lucu C, Müller I, Uhlenbruck G (1981) Lectin, a possible basis for symbiosis between bacteria and sponges. J Bacteriol 145:548–558PubMedGoogle Scholar
  50. Murakawa M, Jung SK, Iijima K, Yonehara S (2001) Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms. Cell Death Differ 8:298–307PubMedCrossRefGoogle Scholar
  51. Mutou T, Kondo T, Ojika M, Yamada K (1996) Isolation and stereostructures of dolastatin G and nordolastatin G, cytotoxic 35-membered cyclodepsipeptides from the Japanese sea hare Dolabella auricularia. J Org Chem 61:6340–6345PubMedCrossRefGoogle Scholar
  52. Nakao Y, Yoshida WY, Takada Y, Kimura J, Yang L, Mooberry SL, Scheuer PJ (2004)Google Scholar
  53. Kulokekahilide-2, a cytotoxic depsipeptide from a cephalaspidean mollusk Philinopsis speciosa. J Nat Prod 67:1332–1340Google Scholar
  54. Nolen T, Johnson P (2001) Defensive inking in Aplysia spp: multiple episodes of ink secretion and the adaptive use of a limited chemical resource. J Exp Biol 204:1257–1268PubMedGoogle Scholar
  55. Nolen T, Johnson P, Kicklighter C, Capo T (1995) Ink secretion by the marine snail Aplysia californica enhances its ability to escape from a natural predator. J Comp Physiol 176A:239–254Google Scholar
  56. Obara K, Otsuka-Fuchino H, Sattayasai N, Nonomura Y, Tsuchiya T, Tamiya T (1992) Molecular cloning of the antibacterial protein of the giant African snail, Achatina fulica Ferussac. Eur J Biochem 209:1–6PubMedCrossRefGoogle Scholar
  57. Ojika M, Nemoto T, Nakamura M, Yamada K (1995) Dolastatin E, a new cyclic hexapeptide isolated from the sea hare Dolabella auricularia. Tetrahedron Lett 36:5057–5058Google Scholar
  58. Otsuka-Fuchino H, Watanabe Y, Hirakawa C, Tamiya T, Matsumoto J, Tsuchiya T (1992) Bactericidal action of a glycoprotein from the body surface mucus of giant African snail. Comp Biochem Physiol C 101:607–613PubMedGoogle Scholar
  59. Ozeki Y (1998) Purification and cell attachment activity of a D-galactose-binding lectin from the skin of sea hare, Aplysia kurodai. Biochem Mol Biol Int 45:989–995PubMedGoogle Scholar
  60. Painter SD, Cummins SF, Nichols AE, Akalal DB, Schein CH, Braun W, Smith JS, Susswein AJ, Levy M, de Boer PA, ter Maat A, Miller MW, Scanlan C, Milberg RM, Sweedler JV, Nagle GT (2004) Structural and functional analysis of Aplysia attractins, a family of waterborne protein pheromones with interspecific attractiveness. Proc Natl Acad Sci USA 101:6929–6933PubMedCrossRefGoogle Scholar
  61. Pauley GB, Krassner SM, Chapman FA (1971) Bacterial clearance in the California sea hare, Aplysia californica. J Invertebr Pathol 18:227–239PubMedCrossRefGoogle Scholar
  62. Pettit GR (1997) The dolastatins. Fortschr Chem Org Naturst 70:1–79PubMedGoogle Scholar
  63. Pettit GR, Xu JP, Doubek DL, Chapuis JC, Schmidt JM (2004) Antineoplastic agents. 510. Isolation and structure of dolastatin 19 from the Gulf of California sea hare Dolabella auricularia. J Nat Prod 67:1252–1255PubMedCrossRefGoogle Scholar
  64. Petzelt C, Joswig G, Stammer H, Werner D (2002) Cytotoxic cyplasin of the sea hare, Aplysia punctata, cDNA cloning, and expression of bioactive recombinants in insect cells. Neoplasia 4:49–59PubMedCrossRefGoogle Scholar
  65. Poncet J (1999) The dolastatins, a family of promising antineoplastic agents. Curr Pharm Des 5:139–162PubMedGoogle Scholar
  66. Ponnudurai G, Chung MC, Tan NH (1994) Purification and properties of the L-amino acid oxidase from Malayan pit viper (Calloselasma rhodostoma) venom. Arch Biochem Biophys 313:373–378PubMedCrossRefGoogle Scholar
  67. Rajaganapathi J, Kathiresan K, Singh TP (2002) Purification of anti-HIV protein from purple fluid of the sea hare Bursatella leachii de Blainville. Mar Biotechnol 4:447–453PubMedCrossRefGoogle Scholar
  68. Rao J, Li N (2004) Microfilament actin remodeling as a potential target for cancer drug development. Curr Cancer Drug Targets 4:345–354PubMedCrossRefGoogle Scholar
  69. Rolff J, Siva-Jothy MT (2004) Selection on insect immunity in the wild. Proc R Soc Lond B Biol Sci 271:2157–2160CrossRefGoogle Scholar
  70. Saito S, Watabe S, Ozaki H, Fusetani N, Karaki H (1994) Mycalolide B, a novel actin depolymerizing agent. J Biol Chem 269:29710–29714PubMedGoogle Scholar
  71. Saito S, Watabe S, Ozaki H, Kigoshi H, Yamada K, Fusetani N, Karaki H (1996) Novel actin depolymerizing macrolide aplyronine A. J Biochem 120:552–555PubMedGoogle Scholar
  72. Saito SY, Feng J, Kira A, Kobayashi J, Ohizumi Y (2004) Amphidinolide H, a novel type of actin-stabilizing agent isolated from dinoflagellate. Biochem Biophys Res Commun 320:961–965PubMedCrossRefGoogle Scholar
  73. Sakamoto Y, Nakajima T, Misawa S, Ishikawa H, Itoh Y, Nakashima T, Okanoue T, Kashima K, Tsuji T (1998) Acute liver damage with characteristic apoptotic hepatocytes by ingestion of Aplysia kurodai, a sea hare. Intern Med 37:927–929PubMedCrossRefGoogle Scholar
  74. Schwartsmann G, Brondani da Rocha A, Berlinck RG, Jimeno J (2001) Marine organisms as a source of new anticancer agents. Lancet Oncol 2:221–225PubMedCrossRefGoogle Scholar
  75. Sone H, Nemoto T, Ojika M, Yamada K (1993a) Isolation, structure and synthesis of dolastatin C, a new depsipeptide from the sea hare Dolabella auricularia. Tetrahedron Lett 34:8445–8448CrossRefGoogle Scholar
  76. Sone H, Nemoto T, Ishiwata H, Ojika M, Yamada K (1993b) Isolation, structure and synthesis of dolastatin D, a cytotoxic cyclic depsipeptide from the sea hare Dolabella auricularia. Tetrahedron Lett 34:8499–8452Google Scholar
  77. Sone H, Kondo T, Kiryu M, Ishiwata H, Ojika M, Yamada K (1995) Dolabellin, a cytotoxic bisthiazole isolated from the sea hare Dolabella auricuralia: structure determination and synthesis. J Org Chem 60:4774–4781CrossRefGoogle Scholar
  78. Sone H, Shibata T, Fujita T, Ojika M, Yamada K (1996a) Dolastatin H and isodolastatin H, potent cytotoxic peptides from sea hare Dolabella auricularia: isolation, stereostructure and synthesis. J Am Chem Soc 118:1874–1880CrossRefGoogle Scholar
  79. Sone H, Kigoshi H, Yamada K (1996b) Auriside A and B, cytotoxic macrolide glycosides from the Japanese sea hare Dolabella auricularia. J Org Chem 61:8956–8960PubMedCrossRefGoogle Scholar
  80. Sone H, Kigoshi H, Yamada K (1997) Isolation and stereostructure of dolastatin I, a cytotoxic cyclic hexapeptide from the Japanese sea hare Dolabella auricularia. Tetrahedron 53:8149–8154CrossRefGoogle Scholar
  81. Sorokin M (1988) Human poisoning by ingestion of a sea hare (Dolabella auricularia). Toxicon 26:1095–1097PubMedCrossRefGoogle Scholar
  82. Spector I, Shochet NR, Kashman Y, Groweiss A (1983) Latrunculins: novel marine toxins that disrupt microfilament organization in cultured cells. Science 219:493–495PubMedCrossRefGoogle Scholar
  83. Suenaga K, Mutou T, Shibata T, Itoh T, Kigoshi H, Yamada K (1996) Isolation and stereostructure of aurilide, a novel cyclodepsipeptide from the Japanese sea hare Dolabella auricularia. Tetrahedron 53:8149–8154Google Scholar
  84. Suenaga K, Kamei N, Okugawa Y, Takagi M, Akao A, Kigoshi H, Yamada K (1997) Cytotoxicity and actin depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and the natural and artificial analogs. Bioorg Med Chem Lett 7:269–274CrossRefGoogle Scholar
  85. Suenaga K, Mutou T, Shibata T, Itoh T, Fujita T, Takada N, Hayamizu K, Takagi M, Irifune T, Kigoshi H, Yamada K (2004) Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity. Tetrahedron 60:8509–8527CrossRefGoogle Scholar
  86. Suhr SM, Kim DS (1999) Comparison of the apoptotic pathways induced by L-amino acid oxidase and hydrogen peroxide. J Biochem 125:305–309PubMedGoogle Scholar
  87. Sun Y, Nonobe E, Kobayashi Y, Kuraishi T, Aoki F, Yamamoto K, Sakai S (2002) Characterization and expression of L-amino acid oxidase of mouse milk. J Biol Chem 277:19080–19086PubMedCrossRefGoogle Scholar
  88. Takamatsu N, Shiba T, Muramoto K, Kamiya H (1995) Molecular cloning of the defense factor in the albumen gland of the sea hare Aplysia kurodai. FEBS Lett 377:373–376PubMedCrossRefGoogle Scholar
  89. Takeuchi H, Ara G, Sausville EA, Teicher B (1998) Jasplakinolide: interaction with radiation and hyperthermia in human prostate carcinoma and Lewis lung carcinoma. Cancer Chemother Pharmacol 42:491–496PubMedCrossRefGoogle Scholar
  90. Tan NH, Saifuddin MN (1991) Substrate specificity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase. Int J Biochem 23:323–327PubMedCrossRefGoogle Scholar
  91. Tanaka J, Yan Y, Choi J, Bai J, Klenchin VA, Rayment I, Marriott G (2003) Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides. Proc Natl Acad Sci USA 100:13851–13856PubMedCrossRefGoogle Scholar
  92. Tchang S, Lin G (1964) A study on Aplysiidae from China coast (in Chinese). Stud Mar Sin 5:1–25Google Scholar
  93. Terry DR, Spector I, Higa T, Bubb MR (1997) Misakinolide A is a marine macrolide that caps but does not sever filamentous actin. J Biol Chem 272:7841–7845PubMedCrossRefGoogle Scholar
  94. Torii S, Naito M, Tsuruo T (1997) Apoxin I, a novel apoptosis-inducing factor with L-amino acid oxidase activity purified from Western diamondback rattlesnake venom. J Biol Chem 272:9539–9542PubMedCrossRefGoogle Scholar
  95. Vallon O (2000) New sequence motifs in flavoproteins: evidence for common ancestry and tools to predict structure. Proteins 38:95–114PubMedCrossRefGoogle Scholar
  96. Vasta R (1991) The multiple biological roles of invertebrate lectins: their participation in nonself recognition mechanism. In: Warr G, Cohen N (eds) Phylogenesis of immune functions. CRC, Boston, pp 73–101Google Scholar
  97. Weiss KR, Brezina V, Cropper EC, Heierhorst J, Hooper SL, Probst WC, Rosen SC, Vilim FS, Kupfermann I (1993) Physiology and biochemistry of peptidergic cotransmission in Aplysia. J Physiol 87:141–151Google Scholar
  98. Whim MD, Church PJ, Lloyd PE (1993) Functional roles of peptide cotransmitters at neuromuscular synapses in Aplysia. Mol Neurobiol 7:335–347PubMedCrossRefGoogle Scholar
  99. Wilson MP, Carrow GM, Levitan IB (1992) Modulation of growth of Aplysia neurons by an endogenous lectin. J Neurobiol 23:739–750PubMedCrossRefGoogle Scholar
  100. Wu AM, Song SC, Chen YY, Gilboa-Garber N (2000) Defining the carbohydrate specificities of aplysia gonad lectin exhibiting a peculiar D-galacturonic acid affinity. J Biol Chem 275:14017–14024PubMedCrossRefGoogle Scholar
  101. Yamada K, Kigoshi H (1997) Bioactive compounds from the sea hares of two genera Aplysia and Dolabella. Bull Chem Soc Jpn 70:1479–1489CrossRefGoogle Scholar
  102. Yamada K, Ojika M, Ishigaki T, Yoshida Y, Ekimoto H, Arakawa M (1993) Aplyronine A, a potent antitumor substance, and the congeners aplyronine B and C isolated from the sea hare Aplysia kirodai. J Am Chem Soc 115:11020–11021CrossRefGoogle Scholar
  103. Yamada K, Ojika M, Kigoshi H, Suenaga K (2000) Cytotoxic substances from opisthobranch mollusks. In: Fusetani N (ed) Drugs from the sea. Kargar, Basel, pp 59–73CrossRefGoogle Scholar
  104. Yamamura S, Hirata Y (1963) Structures of aplysin and aplysinol, naturally occurring bromocompounds. Tetrahedron 19:1485–1496CrossRefGoogle Scholar
  105. Yamazaki M (1993) Antitumor and antimicrobial glycoproteins from sea hares. Comp Biochem Physiol C 105:141–146PubMedCrossRefGoogle Scholar
  106. Yamazaki M, Kisugi J, Kimura K, Kamiya H, Mizuno D (1985) Purification of antineoplastic factor from eggs of a sea hare. FEBS Lett 185:295–298PubMedCrossRefGoogle Scholar
  107. Yamazaki M, Kimura K, Kisugi J, Kamiya H (1986) Purification of a cytolytic facter from purple fluid of a sea hare. FEBS Lett 198:25–28CrossRefGoogle Scholar
  108. Yamazaki M, Kimura K, Kisugi J, Muramoto K, Kamiya H (1989a) Isolation and characterization of a novel cytolytic factor in purple fluid of the sea hare, Aplysiakurodai. Cancer Res 49:3834–3838 PubMedGoogle Scholar
  109. Yamazaki M, Kisugi J, Kamiya H (1989b) Biopolymers from marine invertebrates. XI. Characterization of an antineoplastic glycoprotein, dolabellanin A, from the albumen gland of a sea hare, Dolabella auricularia. Chem Pharm Bull 37:3343–3346PubMedGoogle Scholar
  110. Yamazaki M, Tansho S, Kisugi J, Muramoto K, Kamiya H (1989c) Purification and characterization of a cytolytic protein from purple fluid of the sea hare, Dolabella auricularia. Chem Pharm Bull 37:2179–2182PubMedGoogle Scholar
  111. Zhang X, Minale L, Zampella A, Smith CD (1997) Microfilament depletion and circumvention of multiple drug resistance by sphinxolides. Cancer Res 57:3751–3758PubMedGoogle Scholar
  112. Zhang H, Teng M, Niu L, Wang Y, Wang Y, Liu Q, Huang Q, Hao Q, Dong Y, Liu P (2004) Purification, partial characterization, crystallization and structural determination of AHP-LAAO, a novel L-amino-acid oxidase with cell apoptosis-inducing activity from Agkistrodon halys pallas venom. Acta Crystallogr D Biol Crystallogr 60:974–977PubMedCrossRefGoogle Scholar
  113. Zhou ZH, Komiyama M, Terao K, Shimada Y (1994) Effects of pectenotoxin-1 on liver cells in vitro. Nat Toxins 2:132–135PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.School of Fisheries SciencesKitasato UniversityIwateJapan

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