Elizabeth Escobar Díaz *

Autora invitada por SIIC

Este trabajo contribuye a la investigación de nuevas drogas con actividad antitumoral obtenidas de bacterias como Serratia marcescens

UN NUEVO CICLODEPSIPEPTIDO AT514 INDUCE APOPTOSIS EN CELULAS DE LEUCEMIA LINFOCITICA CRONICA B

Por su gran actividad antitumoral, este nuevo ciclodepsipéptido –AT514– podría ser usado como una alternativa para el tratamiento de la LLC-B, ya sea solo o combinado con otras drogas, sobre todo en aquellos casos donde se observa resistencia al tratamiento convencional.

*Elizabeth Escobar Díaz
describe para SIIC los aspectos relevantes de su trabajo
AT514, A CYCLIC DEPSIPEPTIDE FROM SERRATIA MARCESCENS, INDUCES APOPTOSIS OF B-CHRONIC LYMPHOCYTIC LEUKEMIA CELLS: INTERFERENCE WITH THE AKT/NF-KAPPAB SURVIVAL PATHWAY
Institución principal de la investigación
*Centro de Investigaciones Biológicas CSIC, Madrid, España
Imprimir nota

Comprar este artículo
Otros artículos escogidos

Referencias bibliográficas
1. Kroft SH, Finn WG, Peterson LC. The pathology of the chronic lymphoid leukaemias. Blood Rev 1995; 9:234-250.
2. Bannerji R, Byrd JC. Update on the biology of chronic lymphocytic leukemia. Curr Opin Oncol 1998; 12:22-29.
3. Jewell AP. Role of apoptosis in the pathogenesis of B-cell chronic lymphocytic leukaemia. Br J Biomed Sci 2002; 59:235-238.
4. Barragán M, Bellosillo B, Campas C, Colomer D, Pons G, Gil J. Involvement of protein kinase C and phosphatidyl-inositol 3-kinase pathways in the survival of chronic lymphocytic leukemia cells. Blood 2002; 99:2969-2976.
5. Ringshausen I, Schneller F, Bogner C, Hipp S, Duyster J, Peschel C et al. Constitutively activated phosphatidyl-inositol 3-kinase (PI3-K) is involved in the effect of apoptosis in B-CLL: association with protein kinase C . Blood 2002; 100:3741-3748.
6. Cuní S, Pérez-Aciego P, Pérez-Chacón G, Vargas JA, Sánchez A, Martín-Saavedra FM et al. A sustained activation of PI3K/NF- B pathway is critical for the survival of chronic lymphocytic leukemia B cells. Leukemia 2004; 18:1391-1400.
7. Furman RR, Asgary Z, Mascarenhas JO, Liou HC, Schattner EJ. Modulation of NF- B activity and apoptosis in chronic lymphocytic leukemia B cells. J Immunol 2000; 164:2200-2206.
8. Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. Bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993; 82:1820-1828.
9. Pepper C, Hoy T, Bentley DP. Bcl-2/Bax ratios in chronic lymphocytic leukemia and their correlation with in vitro and clinical drug resistance. Br J Cancer 1997; 76:935-938.
10. Thomas A, El Rouby S, Reed JC, Krajewsky S, Silber R, Potmesil M et al. Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: relationship between p53 mutations and bcl-2/bax proteins in drug resistance. Oncogene 1996; 12:1055-1062.
11. Schriever F, Huhn D. New directions in the diagnosis and treatment of chronic lymphocytic leukaemia. Drugs 2003; 63:953-969.
12. Ballard CE, Yu H, Wang B. Recent developments in depsipeptide research. Curr Med Chem 2002; 9:471-498.
13. Khan SB, Maududi T, Barton K, Ayers J, Alkan S. Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma. Br J Haematol 2004; 125:156-161.
14. Byrd JC, Shinn C, Ravi R, Willis CR, Waselenko JK, Flinn IW et al. Depsipeptide (FR901228): a novel therapeutic agent with selective, in vitro activity against human B-cell chronic lymphocytic leukemia cells. Blood 1999; 94:1401-1408.
15. Aron JL, Parthun MR, Marcucci G, Kitada S, Mone AP, Davis ME et al.. Depsipeptide FR901228 induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood 2003; 102:652-658.
16. Bar-Ness R, Avrahamy N, Matsuyama T, Rosenberg M. Increased cell surface hydrophobicity of a Serratia marcescens NS 38 mutant lacking wetting activity. J Bacteriol 1988; 170:4361-4364.
17. Millet I, Phillips RJ, Sherwin RS, Ghosh S, Voll RE, Flavell RA et al.. Inhibition of NF- B activity and enhancement of apoptosis by the neuropeptide calcitonin gene-related peptide. J Biol Chem 2000; 275:15114-15121.
18. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997; 326:1-16.
19. Kane LP, Shapiro VS, Stokoe D, Weiss A. Induction of NF- B by the Akt/PKB kinase. Curr Biol 1999; 9:601-604.
20. Madrid LV, Wang CY, Gurrtidge DC, Schottelius AJ, Baldwin S, Mayo MW. Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF- B. Mol Cell Biol 2000; 20:1626-1638.
21. Yano O, Kanellopoulos J, Kieran M, Le Bail O, Israel A, Kourilsky P. Purification of KBF1, a common factor binding to both H-2 and beta 2-microglobulin enhancers. EMBO J 1987; 6:3317-3324.
22. Bellosillo B, Villamor N, Colomer D, Pons G, Montserrat E, Gil J. In vitro evaluation of fludarabine in combination with cyclophosphamide and/or mitoxantrone in B-cell chronic lymphocytic leukemia. Blood 1999; 94:2836-2843.
23. De la Fuente MT, Casanova B, Cantero E, Hernández del Cerro M, García-Marco J, Silva A et al. Involvement of p53 in 4 1 integrin-mediated resistance of B-CLL cells to fludarabine. Biochem Biophys Res Comm 2003; 311:708-712.
24. Jones DT, Ganeshaguru K, Virchis AE, Folarin NI, Lowdell MW, Mehta AB et al. Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or radiation. Blood 2001; 98:2800-2807.
25. Moon EY, Adam L. PDE4 inhibitors activate a mitochondrial apoptotic pathway in chronic lymphocytic leukemia cells that is regulated by protein phosphatase 2A. Blood 2003; 101:4122-4130.
26. Decker T, Oelsner M, Kreitman RJ, Salvatore G, Wang Q-C, Pastan I et al. Induction of caspase-dependent programmed cell death in B-cell chronic lymphocytic leukemia by anti-CD22 immunotoxins. Blood 2004; 103:2718-2726.
27. Campas C, López JM, Santidrián AF, Barragán M, Bellosillo B, Colomer D et al. Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 2003; 101:3674-3680.
28. Lucas DM, Davis ME, Parthun MR, Mone AP, Kitada S, Cunningham KD et al. The histone deacetylase inhibitor MS-275 induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia 2004; 18:1207-1214.
29. Jones DT, Ganeshaguru K, Anderson RJ, Jackson TR, Bruckdorfer KR, Low SY et al. Albumin activates the Akt signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil-and radiation-induced apoptosis. Blood 2003; 101:3174-3180.
30. Kandel ES, Hay N. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp Cell Res 1999; 253:210-229.
31. Fecteau KA, Mei J, Wang H-CR. Differential modulation of signalling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228. J Pharmacol Exp Ther 2002; 300:890-899.
32. Burstein E, Duckett CS. Dying for NF- B? Control of cell death by transcriptional regulation of the apoptotic machinery. Curr Opin Cell Biol 2003; 15:732-737.
33. Dewson G, Snowden RT, Almond JB, Dyer MJS, Cohen GM. Conformational change and mitochondrial translocation of Bax accompany proteasome inhibitor-induced apoptosis of chronic lymphocytic leukemic cells. Oncogene 2003; 22:2643-2654.
34. Yamaguchi H, Wang HG. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene 2001; 20:7779-7786.
35. Tsuruta F, Masuyama N, Gotoh Y. The phosphatidylinositol 3-kinase (PI3-K)-Akt pathway suppresses Bax translocation to mitochondria. J Biol Chem 2002; 277:14040-14047.
36. Senderowicz AM. Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr Opin Cell Biol 2004; 16:670-678.