Antitumor activity of cucumarioside A2-2

The cytotoxic activity of sea cucumber glycosides against different types of cells and cell lines, including human tumor cell lines, has been studied for many years. However, the molecular mechanism(s) of the antitumor action of triterpene glycosides on cancer cells remain unclear. This article repo...

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Bibliographic Details
Published in:	Chemotherapy (Basel) Vol. 59; no. 3; p. 181
Main Authors:	Menchinskaya, E S, Pislyagin, E A, Kovalchyk, S N, Davydova, V N, Silchenko, A S, Avilov, S A, Kalinin, V I, Aminin, D L
Format:	Journal Article
Language:	English
Published:	Switzerland 01-01-2014
Subjects:	Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Carcinoma, Ehrlich Tumor - drug therapy Carcinoma, Ehrlich Tumor - mortality Carcinoma, Ehrlich Tumor - pathology Cell Line, Tumor Cell Survival - drug effects DNA - metabolism Humans Kaplan-Meier Estimate Mice S Phase Cell Cycle Checkpoints - drug effects Saponins - chemistry Saponins - pharmacology Saponins - therapeutic use Sea Cucumbers - chemistry Sea Cucumbers - metabolism Transplantation, Homologous Tumor Suppressor Protein p53 - metabolism
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Summary:	The cytotoxic activity of sea cucumber glycosides against different types of cells and cell lines, including human tumor cell lines, has been studied for many years. However, the molecular mechanism(s) of the antitumor action of triterpene glycosides on cancer cells remain unclear. This article reports a continuation of investigations of triterpene glycoside cucumarioside A2-2 isolated from the Far-Eastern sea cucumber Cucumaria japonica. It describes a study of glycoside anticancer activity in vivo and glycoside interaction with mouse Ehrlich carcinoma cells in vitro. The cytotoxicity of cucumarioside A2-2 and its effect on apoptosis, the cell cycle, DNA biosynthesis and p53 activity, and glycoside anticancer action against Ehrlich carcinoma cells were studied. Cucumarioside A2-2 influences tumor cell viability at micromolar concentrations. The EC50 for glycoside estimated by nonspecific esterase assay and MTT assay was 2.1 and 2.7 μM, respectively. Cucumarioside A2-2 at a subcytotoxic range of concentrations exhibits a cytostatic effect by blocking cell proliferation and DNA biosynthesis in the S phase. It may induce apoptosis in tumor cells in a caspase-dependent way, bypassing the activation of the p53-dependent segment. The anticancer and proapoptotic properties of cucumarioside A2-2 may be due to direct interaction of the glycoside with tumor cells. The in vivo anticancer effect of cucumarioside A2-2 may be associated with the ability of the drug to arrest the cell cycle in the synthetic phase and induce programmed tumor cell death.
ISSN:	1421-9794
DOI:	10.1159/000354156