G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Division of the Russian Academy of Sciences, Vladivostok, Russia.
Chemotherapy. 2013;59(3):181-91. doi: 10.1159/000354156. Epub 2013 Nov 8.
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.
多年来，人们一直在研究海参糖苷对不同类型的细胞和细胞系（包括人类肿瘤细胞系）的细胞毒性作用。然而，三萜糖苷对癌细胞的抗肿瘤作用的分子机制尚不清楚。本文报道了对从远东海参（Cucumaria japonica）中分离出的三萜糖苷 cucumarioside A2-2 的进一步研究。它描述了糖苷在体内的抗癌活性以及糖苷与小鼠 Ehrlich 癌细胞在体外的相互作用的研究。
研究了 cucumarioside A2-2 的细胞毒性及其对细胞凋亡、细胞周期、DNA 生物合成和 p53 活性的影响，以及糖苷对 Ehrlich 癌细胞的抗癌作用。
Cucumarioside A2-2 在微摩尔浓度下影响肿瘤细胞活力。通过非特异性酯酶测定和 MTT 测定，糖苷的 EC50 值分别为 2.1 和 2.7 μM。Cucumarioside A2-2 在亚细胞毒性浓度范围内通过阻断 S 期细胞增殖和 DNA 生物合成表现出细胞抑制作用。它可能通过依赖半胱天冬酶的方式诱导肿瘤细胞凋亡，绕过 p53 依赖性途径的激活。
Cucumarioside A2-2 的抗癌和促凋亡特性可能归因于糖苷与肿瘤细胞的直接相互作用。Cucumarioside A2-2 的体内抗癌作用可能与药物能够在合成期阻止细胞周期并诱导程序性肿瘤细胞死亡的能力有关。
