Involvement of BID Translocation in Glycyrrhetinic Acid and 11-Deoxy Glycyrrhetinic Acid-Induced Attenuation of Gastric Cancer Growth
Involvement of BID Translocation in Glycyrrhetinic Acid and 11-Deoxy Glycyrrhetinic Acid-Induced Attenuation of Gastric Cancer Growth
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BID 易位参与甘草次酸和 11-脱氧甘草次酸诱导的胃癌生长减弱
DOI：
10.1080/01635581.2013.877498
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发表时间：
2014-04-03
影响因子：
2.9
通讯作者：
Hu, Tianhui
中科院分区：
文献类型：
--
作者：
Lin, Dejian;Zhong, Wei;Hu, Tianhui
甘草次酸（GA）是甘草的主要化学成分，具有显著的抗癌活性。然而，它的副作用限制了它的广泛使用。11-DOGA通过将GA 11-羰基还原为11-羟基来产生，以减少其副作用，尽管其抗癌活性在很大程度上是未知的。本文就GA和11-DOGA在胃癌中的作用机制以及两种药物的药理潜力进行了比较。首先，我们发现GA和11-DOGA以剂量和时间依赖的方式显著抑制胃癌细胞的活力。GA和11-DOGA均通过上调p21、下调cdc 2和cyclin B1的表达诱导胃癌细胞凋亡并使细胞周期阻滞于G2期。进一步的研究表明，GA和11-DOGA诱导的胃癌细胞凋亡与BID从细胞核向线粒体的移位有关。GA和11-DOGA能有效抑制胃癌细胞裸鼠成瘤。与11-DOGA相比，GA在体内外对胃癌细胞的毒性均较高。因此，GA和11-DOGA诱导的胃癌生长衰减的功能机制的阐明表明GA及其衍生物的可能的治疗作用。
Glycyrrhetinic acid (GA), the main chemical constituents of licorice, has shown remarkable anticancer activity. However, the side effects limit its widespread use. 11-DOGA is produced through reduction of GA 11-carbonyl to 11-hydroxyl to reduce its side effects, although its anticancer activities are largely unknown. Here, we report that the functional mechanisms of GA and 11-DOGA in gastric cancers, as well as the comparison between these two drugs’ pharmacological potential. Firstly, we found that GA and 11-DOGA significantly inhibits the viabilities of gastric cancer cells in dose- and time-dependent manners. Both GA and 11-DOGA induce gastric cancer cells apoptosis and cell cycle arrest in G2 phase by upregulation of p21 and downregulation of cdc2 and cyclin B1. Further studies show that GA and 11-DOGA-induced apoptosis in gastric cancer cells is associated with BID translocation from nucleus to mitochondria. Moreover, GA and 11-DOGA could effectively inhibit tumor formation of gastric cancer cells in nude mice. Comparing with 11-DOGA, GA presents higher toxicity toward gastric cancer cells both in vivo and in vitro. Thus, the elucidation of the functional mechanisms of GA and 11-DOGA-induced attenuation of gastric cancer growth suggests a possible therapeutic role of GA and its derivatives.