Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
Department of Biosciences, Biotechnology and Pharmacological Sciences, University of Bari, via Orabona 4, 70100 Bari, Italy.
Chem Biol Interact. 2015 Jul 25;237:1-8. doi: 10.1016/j.cbi.2015.05.005. Epub 2015 May 14.
Anigopreissin A belongs to stilbene di- and oligomeric forms containing a benzofuran ring system whose biological activity is unknown. Recently, a completely protected Anigopreissin A - Permethylated Anigopreissin A - has been synthesized. We use MTT bioassay to assess Permethylated Anigopreissin A cytotoxicity in different human cell lines. Furthermore, fluorescence microscopy, caspase activity, real-time PCR and Western-blot methods are employed to evaluate apoptotic cell death pathway in liver cancer cells. Permethylated Anigopreissin A kills different types of human cancer cells but does not affect non-tumorigenic cells. The Permethylated Anigopreissin A concentration that causes 50% inhibition of liver tumor cells is 0.24μM. Hepatoma cells treated with Permethylated Anigopreissin A arrest their cell cycle in G1 phase. We also demonstrate that Permethylated Anigopreissin A-triggered cell death occurs by apoptosis. Decrease of the BCL2 expression levels, loss of the mitochondrial membrane potential, release of cytochrome c and increase of caspase 9 activity highlight a key role for mitochondria in Permethylated Anigopreissin A-induced apoptosis. Our study shows that Permethylated Anigopreissin A kills liver cancer cells through intrinsic apoptotic pathway.
阿尼戈普雷斯辛 A 属于二聚体和多聚体形式的芪类，含有苯并呋喃环系统，其生物活性未知。最近，一种完全保护的阿尼戈普雷斯辛 A - 全甲基化阿尼戈普雷斯辛 A - 已经被合成。我们使用 MTT 生物测定法来评估不同人类细胞系中全甲基化阿尼戈普雷斯辛 A 的细胞毒性。此外，荧光显微镜、半胱天冬酶活性、实时 PCR 和 Western-blot 方法被用于评估肝癌细胞中的细胞凋亡途径。全甲基化阿尼戈普雷斯辛 A 杀死不同类型的人类癌细胞，但不影响非肿瘤细胞。导致肝癌肿瘤细胞 50%抑制的全甲基化阿尼戈普雷斯辛 A 浓度为 0.24μM。用全甲基化阿尼戈普雷斯辛 A 处理的肝癌细胞使其细胞周期停滞在 G1 期。我们还证明，全甲基化阿尼戈普雷斯辛 A 诱导的细胞死亡是通过细胞凋亡发生的。BCL2 表达水平的降低、线粒体膜电位的丧失、细胞色素 c 的释放和半胱天冬酶 9 活性的增加突出了线粒体在全甲基化阿尼戈普雷斯辛 A 诱导的细胞凋亡中的关键作用。我们的研究表明，全甲基化阿尼戈普雷斯辛 A 通过内在的凋亡途径杀死肝癌细胞。
