Digitoxigenin-3-beta-glucoside通过caspase-9非依赖的线粒体途径诱导人肺腺癌A549细胞凋亡
首发时间:2013-03-01
摘要:目的:暗消藤(Streptocaulon juventas (Lour.) Merr.)属于我国西南地区的特有药用品种,digitoxigenin-3-beta-glucoside(AXT6)为暗消藤主要化学成分。前期研究表明AXT6可通过Fas死亡受体途径诱导人肺腺癌A549细胞凋亡。本论文主要考察AXT6对细胞凋亡过程中线粒体途径的影响。方法:流式细胞术罗丹明染色法考察AXT6对线粒体膜电位的影响;采用Western Blot方法考察AXT6对相关蛋白的影响。结果:AXT6能时间依赖性的降低A549细胞的线粒体膜电位,上调Bax/Bcl-2的比率,下调Sirt-1水平促进Bax从细胞浆向线粒体转位,促进cytochrome c向胞浆释放;但对caspase-9蛋白水平及caspase-9 酶活力均没有显著影响;AXT6呈时间依赖性上调AIF的表达。结论:上述结果表明AXT6诱导了caspase-9 非依赖的线粒体凋亡途径。
关键词: 药理学 digitoxigenin-3-beta-glucoside 凋亡 线粒体途径
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Digitoxigenin-3-beta-glucoside induces human lung carcinoma A549 cell apoptosis through caspase-9 independent mitochondrial pathway
Abstract:Objective: To study the involvement of mitochondrial pathway of apoptosis in human non-small cell lung cancer A549 cells induced by digitoxigenin-3-beta-glucoside (AXT6), an active compound isolated from Chinese folk medicine Streptocaulon juventas (Lour.) Merr.. Method: Rodamine 123 staining and flowcytometric analysis were used to detect AXT6's effect on mitochondrial membrane potential (MMP). Western blotting was used to examine AXT6's effect on protein levels in mitochondrial signaling pathway. Results: AXT6 reduced mitochondrial membranes potential, increased the ratio of Bax/Bcl-2, down-regulated the level of Sirt-1 promoted the translocation of Bax from cytoplasm to mitochondria, and induced the release of cytochrome c from mitochondria into cytoplasm. AXT6 time-dependently up-regulated the expression of AIF. However, it has no effects on caspase-9's protein level and activity. Conclusion: These results indicated that AXT6 induced apoptosis by activating the death receptor pathway and caspase-9-independent mitochondrial pathway.
Keywords: pharmacology digitoxigenin-3-beta-glucoside apoptosis mitochondria pathway
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Digitoxigenin-3-beta-glucoside通过caspase-9非依赖的线粒体途径诱导人肺腺癌A549细胞凋亡
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