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冬凌草甲素 K,一种来自人工栽培桑黄的活性三萜,通过抑制整合素介导的黏附、迁移和侵袭抑制人肝癌细胞转移。

Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood-Cultivated Antrodia cinnamomea, Inhibits Metastasis via Suppression of Integrin-Mediated Adhesion, Migration, and Invasion in Human Hepatoma Cells.

机构信息

ΔDepartment of Food Science, Rutgers University, New Brunswick, New Jersey, United States.

§Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.

出版信息

J Agric Food Chem. 2015 May 13;63(18):4561-9. doi: 10.1021/jf5059304. Epub 2015 May 5.

DOI:10.1021/jf5059304
PMID:25911944
Abstract

Previous research demonstrated that the ethyl acetate extract from Antrodia cinnamomea suppresses the invasive potential of human breast and hepatoma cells, but the effective compounds are not identified. The main bioactive compounds of A. cinnamomea are ergostane-type triterpenoids, and the content of antcin K is the highest. The objective of this study was to evaluate the antimetastatic activity and mechanisms of antcin K purified from the fruiting body of basswood-cultivated A. cinnamomea on human liver cancer Hep 3B cells. The results showed that adhesion, migration, and invasion of Hep 3B cells were effectively inhibited by antcin K within 24 h of treatment. Antcin K not only reduced the protein expression and activity of MMP-2 and MMP-9 but also down-regulated vimentin and up-regulated E-cadherin in Hep 3B cells. In depth investigation for the molecular mechanism revealed that antcin K could reduce the protein expression of integrin β1, β3, α5, and αv and suppress phosphorylation of FAK, Src, PI3K, AKT, MEK, ERK, and JNK. These results suggested that antcin K was able to inhibit the metastasis of human hepatoma cells through suppression of integrin-mediated adhesion, migration, and invasion. Coupled with these findings, antcin K has a good potential to reduce the risk of liver cancer metastasis.

摘要

先前的研究表明,樟芝乙酸乙酯提取物可抑制人乳腺癌和肝癌细胞的侵袭潜力,但有效化合物尚未确定。樟芝的主要生物活性化合物为麦角甾烷型三萜类化合物,其中含量最高的是安特灵 K。本研究旨在评估从白木耳培养的樟芝子实体中纯化的安特灵 K 对人肝癌 Hep 3B 细胞的抗转移活性及其机制。结果表明,安特灵 K 在处理 24 小时内可有效抑制 Hep 3B 细胞的黏附、迁移和侵袭。安特灵 K 不仅降低了 MMP-2 和 MMP-9 的蛋白表达和活性,而且还下调了 Hep 3B 细胞中的波形蛋白并上调了 E-钙黏蛋白。深入研究表明,安特灵 K 可降低整合素 β1、β3、α5 和 αv 的蛋白表达,并抑制 FAK、Src、PI3K、AKT、MEK、ERK 和 JNK 的磷酸化。这些结果表明,安特灵 K 能够通过抑制整合素介导的黏附、迁移和侵袭来抑制人肝癌细胞的转移。结合这些发现,安特灵 K 具有降低肝癌转移风险的良好潜力。

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