Drogas marinas: los animales marinos como fuentes de compuestos antitumorales

Antonio José Laborda Navia, Manuel Martín San Sebastián

Resumen


La evolución ha dotado a muchos organismos marinos con un arsenal de productos químicos que emplean para fines defensivos o sociales. Gracias a esto, las formas de vida marinas constituyen una fuente importante de compuestos bioactivos, implicados hoy en el descubrimiento de nuevas drogas para tratar diversas enfermedades. Miles de esos compuestos han sido ya descubiertos y están siendo evaluados en diversos ensayos biológicos, muchos de ellos en el campo de la oncología. En él, los avances en la determinación de la estructura molecular, síntesis, etc., han permitido que algunos de ellos como citarabina, halaven y yondelis, entre otros, hayan pasado ya a formar parte del mercado farmacéutico. Sin embargo, aún existen limitaciones para explotar todo el potencial de estos compuestos y, en la actualidad, la investigación está dirigida al descubrimiento de nuevas rutas del metabolismo secundario y de novedosas formas de producción sostenible. Además, resulta prioritario el conocimiento de la biodiversidad marina y su conservación, para proteger moléculas de posible interés en el futuro.


Palabras clave


Biología;Biotecnología marina;Cáncer;Fármacos;

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Referencias


Armstrong, J. D., Millidine, K. J. y Metcalfe, N. B. (2011). Ecological consequences of variation in standard metabolism and dominance among salmon. Freshwater Fish, 20: 371–376.

Barr, P. M., Lazarus, H.M. y Cooper, B.W. (2009). Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant. American Journal Hematology, 84: 484-487.

Becerro, M. A., Goetz, A., Paul, V. J. & Scheuer y P. J. (2001). Chemical defenses of the sarcoglossan mollusk Elysia rufescens and its host alga Bryopsis sp. Journal of Chemical Ecology, 27:2287-2299.

Blunt, J. W., Copp, B. R., Munro, M. H. G., Northcote, P. T. y Prinsep, M. R. (2011). Marine natural products. Natural Products Reports, 28:196–268.

Broggini, M., Marchini, S., Galliera, E., Borsotti, P., Taraboletti, G., Erba, E., Sironi, M., Jimeno, J., Faircloth, G. y D'Incalci, M. (2002). Aplidin, a new anticancer agent of marine origin, inhibits VEGF secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemic cells MOLT-4. Leukemia, 17: 52-59.

Ciruelos, E. M., Twelves, C., Dominguez, M. J., McKay, H., Anthony, A., Castellanos, D., Bezares, S., Ruiz, A., Lopez-Lazaro, L., Jimeno, J., Celli, C., Cortes-Funes, H. y Paz-Ares, L. (2002). Phase I clinical and pharmacokinetic study of the marine compound Aplidine (APL) administered as a 3 hour infusion every 2 weeks. American Society of Clinical Oncology 20: 422.

Cooper, G. y Hausman, R. (2000). The cell. Edit: ASM Press and Sinauer Associates, Washington D.C.

Cruz-Monserrate, Z., Mullaney, J., Harran, P., Pettit, G.R. y Hamel, E. (2003). Dolastatin 15 binds in the vinca domain of tubulin as demonstrated by Hummel-Dreyer chromatography. European Journal of Biochemistry, 270: 3822-3828.

Cuadrado, A., García-Fernández, L.F., González, L., Suárez, Y., Losada, A., Alcaide, V., Martínez, T., Fernández-Sousa, J.M., Sánchez-Puelles, J.M. y Muñoz, A. (2003). Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor, Src, JNK and p38 MAPK. The Journal of Biological Chemistry, 278: 241-250.

Dabydeen, D., Florence, G., Paterson, I. y Hamel, E. A. (2004). Quantitative evaluation of the effects of inhibitors of tubulin assembly on polymerization induced by discodermolide, epothilone B, and paclitaxel. Cancer Chemotherapy Pharmacology, 53:397–403.

Davidson, S.K., Allen, S.W., Lim, G.E., Anderson, C.M. y Haygood, M.G. (2001). Evidence for the biosynthesis of bryostatins by the bacterial symbiont 'Candidatus Endobugula sertula' of the bryozoan Bugula neritina. Applied and Environmental Microbiology, 67: 4531–4537.

Gottesman, M.M. (2002). Mechanisms of cancer drug resistance. Annual reviews os Medicine, 53:615–627.

Hamann, M. T. y Scheuer, P.I. (1993). Bioactive peptides from a marine mollusk Elysia rufescens and its algal diet Bryopsis sp. The Journal of Organic Chemistry, 61:6594-6600.

Iwata, S., Sato, Y., Asada, M., Takagi, M., Tsujimoto, A., Inaba, T., Yamada, T., Sakamoto, S., Yata, J., Shimogori, T., Igarashi, K. y Mizutani S. (1999). Antitumor activity of antizyme which targets the ornithine decarboxylase (ODC) required for cell growth and transformation. Oncogene, 18:165-172.

Jensen, P.R., Mincer, T.J., William, P.G. & Fenical, W. (2005). Marine actinomycete diversity and natural product discovery. Antonie van Leeuwenhoek, 87:43-48.

Jha, R.K. y Zi-Rong, X. (2004). Biomedical compounds from marine organisms. Marine Drugs, 2:123–146.

Jimeno, J.M., Faircloth, G., Cameron, L., Meely, K., Vega, E., Gómez, A., Fernández-Sousa, F. y Rinehart, K. (1996). Progress in the acquisition of new marine derived anticancer compounds: Development of Ecteinascidin 743 (Et 743). Drugs from the future, 21(11):1155-1165.

Jordan, M. A. y Wilson, L. (2004). Microtubules as a target for anticancer drugs. Natural Reviems Cancer, 4:253–265.

Katz, J., Janik, J.E. y Younes, A. (2011). Brentuximab Vedotin (SGN-35). Clinical Cancer Research, 17:6428–6436.

Lai, D., Visser-Grieve, S. y Yang, X. (2012). Tumour suppressor genes in chemotherapeutic drug response. Bioscience reports, 32:361-374.

Le Lann, C., Wardziak, T., Van Baaren, J. y Van Alphen, J. J. M. (2010). Thermal plasticity of metabolic rates linked to life-history traits and foraging behaviour in a parasitic wasp. Functional Ecology, 25:641–651.

Lesser, M. P., Slattery, M. y Leichter, J.J. 2009 Ecology of mesophotic coral reefs. Journal of Experimental Marine Biology and Ecology, 375:1–8.

López-Macià, A., Jimenez, J. C., Royo, M., Giralt, E. & Albericio, F. (2001). Synthesis and structure determination of kahalalide F (1,2). Journal of the American Chemical Society, 123:11398-11401.

Luesch, H., Moore, R.E., Paul, V.J., Mooberry, S.L. y Corbett, T.H. (2001). Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. Journal of Natural Products, 64:907–910.

Martínez-Ezquerro, J.D. y Herrera, L.A. (2006). Angiogénesis: VEGF/VEGFRs como blancos terapéuticos en el tratamiento contra el cáncer. Cancerología, 1: 83-96.

Mauroun, J. A., Goel, R., Stewart, D. J., Tomiak, E., Belanger, K., Soulieres, D., Charpentier, D., Seymour, L., Matthews, S., Jimeno, J. y Guzman, C. (2001). Phase I study of Aplidine in a 5 day bolus Q 3 weeks in patients with solid tumors and lymphomas. American Society of Clinical Oncology, 20:2082.

Mayer, A.M., Glaser, K.B., Cuevas, C., Jacobs, R.S., Kem, W., Little, R.D., McIntosh, J.M., Newman, D.J., Potts, B.C. y Shuster, D.E. (2010). The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends in pharmacological science, 31(6):255-265.

Medina, L. A., Gomez, L., Cerna, C., Faircloth, G., Yochmowitz, M. & Weitman, S. (2001). Investigation of the effects of kahalalide F against human tumor specimens taken directly from patients. American Association for Cancer research, 42:1139.

Menis, J. y Twelves, C. (2011). Eribulin (Halaven): a new, effective treatment for women with heavily pretreated metastatic breast cancer. Journal of Breast cáncer: targets and Therapy, 3:101–111.

Miyazaki, K., Kobayashi, M., Natsume, T., Gondo, M., Mikami, T., Sakakibara, K. y Tsukagoshi, S. (1995). Synthesis and antitumor activity of novel dolastatin 10 analogs. Chemical and Pharmaceutical Bulletin, 43:1706–1718.

Moore, K.S., Wehrli, S. y Roder, H. (1993). Squalamine: an aminosterol antibiotic from the shark. Proceedings of the National Academy of Science, 90(4):1354-1358.

Newman, D.J., Cragg, G.M. y Battershill, C.N. (2009). Therapeutic agents from the sea: biodiversity, chemo-evolutionary insight and advances to the end of Darwin's 200th year. Diving and Hyperbaric Medicine Journal, 39:216–225.

Perry, M.C. (2008). The chemotherapy source book. Lippincott Williams & Wilkins, Philadelphia.

Pettit, G.R., Kamano, Y., Herald, C. L, Tuinman, A.A, Boettner, F.E., Kizu, H., Schmidt, J.M., Baczynskyk, L., Tomer, K.B. y Bontems, R.J. (1987). The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin-10. Journal of the American Chemical Society, 109:6883–6885.

Piel, J. (2009). Metabolites from symbiotic bacteria. Natural Products Preports, 26:338–362.

Pomponi, S.A. (1999). The bioprocess-technological potential of the sea. Journal of Biotechnology, 70: 5-13.

Rinehart, K. L. (1994). Pharmaceutical compositions containing didemnins. US Patent No. 5294603:1-25.

Rinehart, K. L. (2000). Antitumor compounds from tunicates. Medicinal research Reviews, 20:1-27.

Rønning, B., Mortensen, A. S., Moe, B., Chastel, O., Arukwe, A. y Bech, C. (2009). Food restriction in young Japanese quails: effects on growth, metabolism, plasma thyroid hormones and mRNA species in the thyroid hormone signalling pathway. The Journal of Experimental Biology, 212:3060– 3067.

Scott, J.D. y Williams, R.M. (2002). Chemistry and biology of the tetrahydroisoquinoline antitumor antibiotics. Chemical review, 102:1669– 1730.

Sills, A.K., Williams, J.L. y Tyler, B.M. (1998). Squalamine inhibits angiogénesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Research, 58:2784-2792.

Thomas, X. (2009). Chemotherapy of acute leukemia in adults. Expert Opinion on Pharmacotherapy, 10:221–237.

Uemura, D., Takahashi, K., Yamamoto, T., Katayama, C., Tanaka, J., Okumura Y. & Hirata, Y. (1985). Norhalichondrin A: an antitumor polyether macrolide from a marine sponge. Journal of the American Chemical Society, 107:4796–4798.

Watanabe, J., Natsume, T. y Kobayashi, M. (2007). Comparison of the antivascular and cytotoxic activities of TZT-1027 (Soblidotin) with those of other anticancer agents. Anticancer, 18:905– 911.

Yeung, B.K.S. (2011). Natural product drug discovery: the successful optimization of ISP-1 and halichondrin B. Current Oponion in Chemical Biology, 15:523–528.

Yun, S.S. y Li, W. (2007). Identification of squalamine in the plasma membrane of white blood cells in the sea lamprey Petromyzon marinus. The Journal of Lipid Research, 48:2579-2586.

http://www.aecc.es/Paginas/PaginaPrincipal.aspx. [Consultada: 28/09/2015]

www.pharmamar.com [Consultada: 10/08/2015]

www.micromedex.com [Consultada: 16/09/2015]




DOI: http://dx.doi.org/10.18002/ambioc.v0i13.4953

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