Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog.
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-kappaB activation.


METHODS
The antiproliferative action of glycosides 1 and 2 were determined on 3 tumor cell lines. Their effect on the activation of NF-kappaB was evaluated by indirect immunofluorescence assay staining and the concomitant IkappaBalpha 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-kappaB, a key player linking chronic inflammation and cancer, concomitant with IkappaBalpha degradation in the A549 tumor cell line. Compounds 1 and 2 showed hemolytic activity with half maximal inhibitory concentration (IC(50)) values around 80 microM.


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 12alpha- and 17alpha-hydroxyl groups and a Delta(7) 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-kappaB. 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.
Careaga
Valeria P
VP
UMYMFOR (CONICET-UBA) y Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Bueno
Carlos
C
Muniain
Claudia
C
Alché
Laura
L
Maier
Marta S
MS
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D053878:Hemolytic Agents / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012616:Sea Cucumbers / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D006027:Glycosides; D053878:Hemolytic Agents; D016328:NF-kappa B; D014315:Triterpenes; C534989:patagonicoside A; C534990:patagonicoside A, desulfated analog