QS-21 和 Quillaja saponaria Molina 中的 quillaic 酸体外评估及其作为胃癌治疗剂的分子对接研究。

In vitro evaluation and molecular docking of QS-21 and quillaic acid from Quillaja saponaria Molina as gastric cancer agents.

机构信息

Laboratorio de Química Biológica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.

Natural Response S.A, Av. Industrial 1970, Quilpué, Región de Valparaíso, Chile.

出版信息

Sci Rep. 2020 Jun 29;10(1):10534. doi: 10.1038/s41598-020-67442-3.

DOI:10.1038/s41598-020-67442-3

PMID:32601436

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7324585/

Abstract

The cytotoxic mechanism of the saponin QS-21 and its aglycone quillaic acid (QA) was studied on human gastric cancer cells (SNU1 and KATO III). Both compounds showed in vitro cytotoxic activity with IC values: 7.1 μM (QS-21) and 13.6 μM (QA) on SNU1 cells; 7.4 μM (QS-21) and 67 μM (QA) on KATO III cells. QS-21 and QA induce apoptosis on SNU1 and KATO III, as demonstrated by TUNEL, Annexin-V and Caspase Assays. Additionally, we performed in silico docking studies simulating the binding of both triterpenic compounds to key proteins involved in apoptotic pathways. The binding energies (∆G) thus calculated, suggest that the pro-apoptotic protein Bid might be a plausible target involved in the apoptotic effect of both triterpenic compounds. Although QA shows some antiproliferative effects on SNU1 cells cultured in vitro, our results suggest that QS-21 is a more powerful antitumor agent, which merits further investigation regarding their properties as potential therapeutic agents for gastric cancer.

摘要

QS-21 及其苷元奎尼酸（QA）的细胞毒性机制在人胃癌细胞（SNU1 和 KATO III）上进行了研究。这两种化合物在体外均表现出细胞毒性活性，其 IC 值为：SNU1 细胞上为 7.1μM（QS-21）和 13.6μM（QA）；KATO III 细胞上为 7.4μM（QS-21）和 67μM（QA）。QS-21 和 QA 通过 TUNEL、Annexin-V 和 Caspase 测定法诱导 SNU1 和 KATO III 细胞凋亡。此外，我们进行了计算机对接研究，模拟了两种三萜类化合物与参与凋亡途径的关键蛋白的结合。由此计算出的结合能（∆G）表明，促凋亡蛋白 Bid 可能是参与两种三萜类化合物促凋亡作用的一个合理靶标。虽然 QA 在体外培养的 SNU1 细胞中表现出一些抗增殖作用，但我们的结果表明，QS-21 是一种更强大的抗肿瘤剂，值得进一步研究其作为胃癌潜在治疗剂的特性。