College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China.
J Sci Food Agric. 2012 Mar 15;92(4):965-74. doi: 10.1002/jsfa.4678. Epub 2011 Oct 19.
Echinoside A (EA) and ds-echinoside A (DSEA) are triterpene glycosides isolated from the sea cucumber Pearsonothuria graeffei. DSEA, the desulfurisation product of EA, has the following structure: β-D-xylopyranosyl-holost-8(9),11(12)-diene-3β,17α-diol. In the present study, we examined the anti-tumour activities-in particular, the structure-activity relationships-of EA and DSEA in vitro and in vivo.
Both EA and DSEA exhibited an inhibitory effect on cell proliferation, along with apoptosis-inducing activity, in HepG2 cells. Moreover, they significantly arrested the cell cycle in the G₀/G₁ phase. A reverse transcriptase-polymerase chain reaction assay revealed that EA and DSEA significantly increased the expression of the cell-cycle-related genes, namely, p16, p21 and c-myc, and decreased that of cyclin D₁. Western blotting analysis demonstrated that they down-regulated the expression of Bcl-2, and enhanced mitochondria cytochrome c release, caspase-3 activation, and poly(adenosine diphosphate ribose) polymerase, cleavage. Nuclear factor kappa B (NF-κB) expression was significantly decreased by DSEA, but was unaffected by EA. EA and DSEA (2.5 mg kg⁻¹) treatment of mice bearing H22 hepatocarcinoma tumours reduced the tumour weight by 49.8% and 55.0%, respectively.
EA and DSEA exhibit marked anti-cancer activity in HepG2 cells, by blocking cell-cycle progression and inducing apoptosis through the mitochondrial pathway. DSEA-induced apoptosis was more potent than EA-induced apoptosis. Furthermore, the two triterpene glycosides derived from P. graeffei may induce apoptosis of HepG2 cells in an NF-κB-dependent or NF-κB-independent manner, depending on their structure.
从海参 Pearsonothuria graeffei 中分离得到的三萜糖苷 Echinoside A（EA）和 ds-echinoside A（DSEA）。DSEA 是 EA 的脱硫产物，其结构如下：β-D-木糖吡喃基-holost-8（9），11（12）-二烯-3β，17α-二醇。本研究考察了 EA 和 DSEA 在体外和体内的抗肿瘤活性，特别是构效关系。
EA 和 DSEA 均对 HepG2 细胞表现出抑制增殖作用，并诱导细胞凋亡。此外，它们还能显著将细胞周期阻滞在 G0/G1 期。逆转录-聚合酶链反应检测表明，EA 和 DSEA 能显著上调细胞周期相关基因 p16、p21 和 c-myc 的表达，下调细胞周期蛋白 D1 的表达。Western blot 分析表明，它们下调 Bcl-2 的表达，并增强线粒体细胞色素 c 释放、caspase-3 激活和多聚（腺嘌呤二核苷酸）聚合酶，切割。DSEA 显著降低核因子 kappa B（NF-κB）的表达，但 EA 对其无影响。EA 和 DSEA（2.5 mg kg-1）处理荷瘤 H22 肝癌小鼠可使肿瘤重量分别减少 49.8%和 55.0%。
EA 和 DSEA 通过阻断细胞周期进程并通过线粒体途径诱导细胞凋亡，在 HepG2 细胞中表现出明显的抗癌活性。DSEA 诱导的凋亡比 EA 诱导的凋亡更有效。此外，两种来源于 P. graeffei 的三萜糖苷可能通过其结构以 NF-κB 依赖或 NF-κB 非依赖的方式诱导 HepG2 细胞凋亡。
