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牛角瓜苷A：一种从牛角瓜中提取的糖苷类萜类化合物通过使细胞周期停滞于G2/M期并表达半胱天冬酶8诱导结肠癌WiDr细胞凋亡。

Calotroposid A: a Glycosides Terpenoids from Calotropis gigantea Induces Apoptosis of Colon Cancer WiDr Cells through Cell Cycle Arrest G2/M and Caspase 8 Expression.

作者信息

Mutiah Roihatul, Widyawaruyanti Aty, Sukardiman Sukardiman

机构信息

Departement of Pharmacy, Faculty of Medical and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Indonesia. Email:

出版信息

Asian Pac J Cancer Prev. 2018 Jun 25;19(6):1457-1464. doi: 10.22034/APJCP.2018.19.6.1457.

DOI:10.22034/APJCP.2018.19.6.1457
PMID:29936715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6103559/
Abstract

Objective: This study aims to isolate the active anticancer compound from ethyl acetate fraction extracted from the roots of Calotropis gigantea and to determine the operating mechanism of the isolates towards WiDr colon cancer cells. Methods: the isolation was conducted by using bioassay guided isolation approach method. The cytotoxic potential was determined by using MTT method. The chemical structure was identified by using UPLCMS/MS and NMR-1H spectroscopy. The cell cycle arrest and apoptosis induction were determined by flow cytometry method. The expression of caspase-8 was determined by immunocytochemistry method. Results: The results showed that the active compounds are obtained calotroposid A compound which is glycosides terpenoids. Calotroposide A is capable of inhibiting the growth of WiDr colon cancer cells at IC50 17.23μg/ml. Cell apoptosis induction took place and was indicated by cell apoptosis increase, S and G2/M accumulation and by caspase-8 expression. Conclusion: Calotroposide A induces anticancer activity against WiDr colon cancer cells by means of apoptosis induction mechanism through extrinsic pathway with increased expression of caspase-8.

摘要

目的

本研究旨在从牛角瓜根中提取的乙酸乙酯部位分离出活性抗癌化合物，并确定分离物对WiDr结肠癌细胞的作用机制。方法：采用生物活性导向分离法进行分离。采用MTT法测定细胞毒性潜力。利用超高效液相色谱-质谱联用仪（UPLCMS/MS）和核磁共振氢谱（NMR-1H）光谱鉴定化学结构。采用流式细胞术测定细胞周期阻滞和凋亡诱导情况。采用免疫细胞化学方法测定半胱天冬酶-8的表达。结果：结果表明，活性化合物为羊角甙A，属于糖苷类萜类化合物。羊角甙A能够抑制WiDr结肠癌细胞的生长，其半数抑制浓度（IC50）为17.23μg/ml。发生了细胞凋亡诱导，表现为细胞凋亡增加、S期和G2/M期积累以及半胱天冬酶-8表达增加。结论：羊角甙A通过外在途径诱导凋亡机制，增加半胱天冬酶-8的表达，从而对WiDr结肠癌细胞产生抗癌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/164d74afc3bb/APJCP-19-1457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/4779b7a0ef07/APJCP-19-1457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/eb07b824ecde/APJCP-19-1457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/ec4091446ced/APJCP-19-1457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/0ec221eb7e2d/APJCP-19-1457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/164d74afc3bb/APJCP-19-1457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/4779b7a0ef07/APJCP-19-1457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/eb07b824ecde/APJCP-19-1457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/ec4091446ced/APJCP-19-1457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/0ec221eb7e2d/APJCP-19-1457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6103559/164d74afc3bb/APJCP-19-1457-g005.jpg

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