20 (R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD), a ginsenoside, was derived from Panax ginseng (C. A. Meyer) and inhibited growth of several cancer cell lines. To improve the anti-cancer activity, we introduced the pyrazine ring to 25-OH-PPD and obtained the compound 20(R)-[2,3-β]-Pyrazine-dammarane-12β,20,25-triol (2-Pyrazine-PPD). we evaluated the anti-cancer activity of 2-Pyrazine-PPD and investigated the main anti-cancer mechanisms of 2-Pyrazine-PPD in gastric cancer cells. We found that 2-Pyrazine-PPD remarkably suppressed the proliferation of gastric cancer cells in a concentration-dependent, and showed little toxicity to the normal cell (human gastric epithelial cell line-GES-1). Further study indicated that 2-Pyrazine-PPD induced apoptosis by mitochondria pathway in BGC-803 cancer cells, and activated unfolded protein response and the protein kinase RNA-activated (PKR)-like ER kinase (PERK)/Eukaryotic translation initiation factor-2α (eIF-2α)/Activating transcription factor 4 (ATF4) axis, the expression level of the protein C/EBP homologous protein (CHOP), the marker of endoplasmic reticulum stress, and the apoptosis inducing by 2-Pyrazine-PPD can partly be inhibited by siRNA-mediated knockdown of CHOP. Moreover, the production of reactive oxygen species was remarkably up-regulated in BGC-803 cancer cells treated with 2-Pyrazine-PPD. N-acetylcysteine (NAC, a reactive oxygen species scavenger) can attenuate 2-Pyrazine-PPD-induced apoptosis and endoplasmic reticulum stress. Taken together, we suggested that 2-Pyrazine-PPD exhibited remarkable anti-cancer activity by reactive oxygen species-mediate cell apoptosis and endoplasmic reticulum stress in gastric cancer cells. Our results uncovered the mechanism of 2-Pyrazine-PPD as a promising anti-tumor candidate for gastric cancer therapy.

20（[R）-Dammarane-3 β，12个β，20％，25四醇（25-OH-PPD），人参皂甙，被来源于人参（CA迈耶）和几种癌细胞系生长抑制。为了提高抗癌活性，我们将吡嗪环引入了25-OH-PPD，获得了化合物20（R）-[2,3- β]-吡嗪-达玛烷-12β，20，25-三醇（2-吡嗪-PPD）。我们评估了2-吡嗪-PPD的抗癌活性，并研究了2-吡嗪-PPD在胃癌细胞中的主要抗癌机制。我们发现2-吡嗪-PPD以浓度依赖性显着抑制胃癌细胞的增殖，并且对正常细胞（人胃上皮细胞系-GES-1）几乎没有毒性。进一步的研究表明2-吡嗪-PPD通过线粒体途径诱导BGC-803癌细胞凋亡，并激活未折叠的蛋白应答和蛋白激酶RNA激活的（PKR）样ER激酶（PERK）/真核翻译起始因子-2α。 （eIF-2α）/激活转录因子4（ATF4）轴，蛋白C / EBP同源蛋白（CHOP）的表达水平，内质网应激的标志物，siRNA介导的CHOP敲低可部分抑制2-吡嗪-PPD诱导的细胞凋亡。此外，在用2-吡嗪-PPD处理的BGC-803癌细胞中，活性氧的产生显着上调。N-乙酰半胱氨酸（NAC，一种活性氧清除剂）可以减轻2-Pyrazine-PPD诱导的细胞凋亡和内质网应激。两者合计，我们建议2-吡嗪-PPD表现出显着的抗癌活性，通过活性氧介导的细胞凋亡和胃癌细胞内质网应激。我们的结果揭示了2-吡嗪-PPD作为胃癌治疗的有希望的抗肿瘤候选物的机制。在用2-吡嗪-PPD处理的BGC-803癌细胞中，活性氧的产生显着上调。N-乙酰半胱氨酸（NAC，一种活性氧清除剂）可以减轻2-Pyrazine-PPD诱导的细胞凋亡和内质网应激。两者合计，我们建议2-吡嗪-PPD表现出显着的抗癌活性，通过活性氧介导的细胞凋亡和胃癌细胞内质网应激。我们的结果揭示了2-吡嗪-PPD作为胃癌治疗的有希望的抗肿瘤候选物的机制。在用2-吡嗪-PPD处理的BGC-803癌细胞中，活性氧的产生显着上调。N-乙酰半胱氨酸（NAC，一种活性氧清除剂）可以减轻2-Pyrazine-PPD诱导的细胞凋亡和内质网应激。两者合计，我们建议2-吡嗪-PPD表现出显着的抗癌活性，通过活性氧介导的细胞凋亡和胃癌细胞内质网应激。我们的结果揭示了2-吡嗪-PPD作为胃癌治疗的有希望的抗肿瘤候选物的机制。我们认为2-吡嗪-PPD在胃癌细胞中通过活性氧介导的细胞凋亡和内质网应激表现出显着的抗癌活性。我们的结果揭示了2-吡嗪-PPD作为胃癌治疗的有希望的抗肿瘤候选物的机制。我们认为2-吡嗪-PPD在胃癌细胞中通过活性氧介导的细胞凋亡和内质网应激表现出显着的抗癌活性。我们的结果揭示了2-吡嗪-PPD作为胃癌治疗的有希望的抗肿瘤候选物的机制。