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Antiproliferative, Cytotoxic and Hemolytic Activities of a Triterpene Glycoside from <i>Psolus patagonicus</i> and Its Desulfated Analog

2008; Karger Publishers; Volume: 55; Issue: 1 Linguagem: Inglês

10.1159/000180340

1421-9794

Valeria P. Careaga, Carlos Alberto Bueno, Claudia Muniaı́n, Laura E. Alché, Marta S. Maier,

Bioactive Compounds and Antitumor Agents

<i>Background:</i> The major triterpene glycoside of the sea cucumber <i>Psolus patagonicus </i>and its desulfated analog were tested for their antiproliferative, cytotoxic and hemolytic activities, and their effect on NF-κB activation. <i>Methods:</i> 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. <i>Results:</i> 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 μ<i>M</i>. <i>Conclusions:</i> 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.