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Abstract:

Background: The major triterpene glycoside of the sea cucumber Psolus patagonicus and its desulfated analog were tested for their antiproliferative, cytotoxic and hemolytic activities, and their effect on NF-κB activation. Methods: The antiproliferative action of glycosides 1 and 2 were determined on 3 tumor cell lines. Their effect on the activation of NF-κB was evaluated by indirect immunofluorescence assay staining and the concomitant IκBα degradation was studied by Western blot. Results: Both compounds were able to suppress the growth of 3 tumor cell lines (Hep3B, MDA-MB231 and A549) and induced the activation of NF-κB, a key player linking chronic inflammation and cancer, concomitant with IκBα degradation in the A549 tumor cell line. Compounds 1 and 2 showed hemolytic activity with half maximal inhibitory concentration (IC50) values around 80 μM. Conclusions: Both glycosides showed low cytotoxic activity in A549 tumor cells in comparison with sea cucumber triterpene glycosides containing a linear tetrasaccharide chain. This could be a result of the uncommon presence of two 12α- and 17α-hydroxyl groups and a Δ7 double bond in the aglycone moiety. This aglycone functionalization may be related to their low membranolytic activity. Although glycosides 1 and 2 exert an antiproliferative effect, their mechanisms of action do not involve inhibition of NF-κB. Recently, it has been shown that diverse and new mechanisms of action are responsible for the antitumor and cytotoxic activities of marine compounds. Therefore, more extensive studies are needed to establish a mechanism of action and to deduce a clear structure-activity relationship of sea cucumber triterpene glycosides. Copyright © 2008 S. Karger AG.

Registro:

Documento: Artículo
Título:Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog
Autor:Careaga, V.P.; Bueno, C.; Muniain, C.; Alché, L.; Maier, M.S.
Filiación:UMYMFOR (CONICET-UBA), Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigación e Ingeniería Ambiental, Universidad Nacional de San Martín, Campus Miguelete, Buenos Aires, Argentina
UMYMFOR (CONICET-UBA), Departamento de Química Orgánica, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Palabras clave:Antiproliferation; Cytotoxicity; Nuclear factor-kappa B; Psolus patagonicus; Sea cucumber; Triterpene glycosides; aglycone; antineoplastic agent; glycoside; hydroxyl group; I kappa B alpha; immunoglobulin enhancer binding protein; patagonicoside a; triterpene derivative; tumor necrosis factor alpha; unclassified drug; animal cell; article; cancer inhibition; cell proliferation; cell viability; chronic inflammation; controlled study; disease association; drug activity; drug cytotoxicity; drug effect; drug isolation; drug mechanism; drug screening; hemolysis; human; human cell; IC 50; immunofluorescence; mouse; nonhuman; priority journal; protein degradation; Psolus patagonicus; sea cucumber; staining; structure activity relation; tumor cell line; Western blotting
Año:2009
Volumen:55
Número:1
Página de inicio:60
Página de fin:68
DOI: http://dx.doi.org/10.1159/000180340
Título revista:Chemotherapy
Título revista abreviado:Chemotherapy
ISSN:00093157
CODEN:CHTHB
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00093157_v55_n1_p60_Careaga

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Citas:

---------- APA ----------
Careaga, V.P., Bueno, C., Muniain, C., Alché, L. & Maier, M.S. (2009) . Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog. Chemotherapy, 55(1), 60-68.
http://dx.doi.org/10.1159/000180340
---------- CHICAGO ----------
Careaga, V.P., Bueno, C., Muniain, C., Alché, L., Maier, M.S. "Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog" . Chemotherapy 55, no. 1 (2009) : 60-68.
http://dx.doi.org/10.1159/000180340
---------- MLA ----------
Careaga, V.P., Bueno, C., Muniain, C., Alché, L., Maier, M.S. "Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog" . Chemotherapy, vol. 55, no. 1, 2009, pp. 60-68.
http://dx.doi.org/10.1159/000180340
---------- VANCOUVER ----------
Careaga, V.P., Bueno, C., Muniain, C., Alché, L., Maier, M.S. Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog. Chemotherapy. 2009;55(1):60-68.
http://dx.doi.org/10.1159/000180340