State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China.
Phytomedicine. 2011 Mar 15;18(5):349-55. doi: 10.1016/j.phymed.2010.08.019. Epub 2010 Oct 29.
In this work, the effects of a pair of positional isomer of ganoderic acids (GAs), namely ganoderic acid Mf (GA-Mf) and ganoderic acid S (GA-S) purified from the fermented mycelia of Ganoderma lucidum, on induction of cell apoptosis and the apoptotic pathway in HeLa cells were investigated. The results demonstrate that both isomers decreased cell population growth on various human carcinoma cell lines by MTT assay, while GA-Mf had better selectivity between normal and cancer cells. The flow cytometry analysis indicated that treatment of HeLa cells with GA-S caused cell cycle arrest in the S phase, while GA-Mf caused cell cycle arrest in the G1 phase. Compared with GA-S, GA-Mf had more potent increase in the number of early and late apoptotic cells. Treatment of HeLa cells with each isomer decreased the mitochondria membrane potential and caused the release of cytochrome c from mitochondria into the cytosol. In addition, stimulation of caspase-3 and caspase-9 activity was observed. The Bax/Bcl-2 ratio was also increased in GA-treated HeLa cells. The results demonstrated that both isomers GA-Mf and GA-S induced apoptosis of human HeLa cells through a mitochondria mediated pathway, but they had the different cell cycle arrest specificity. The findings will be helpful to the development of useful cancer chemopreventive compounds from G. lucidum.
在这项工作中，研究了从灵芝发酵菌丝体中分离得到的一对位置异构体灵芝酸（GAs），即灵芝酸 Mf（GA-Mf）和灵芝酸 S（GA-S）对 HeLa 细胞凋亡诱导和凋亡途径的影响。结果表明，两种异构体均通过 MTT 测定法降低了各种人癌细胞系的细胞群体生长，而 GA-Mf 在正常细胞和癌细胞之间具有更好的选择性。流式细胞术分析表明，GA-S 处理 HeLa 细胞导致细胞周期停滞在 S 期，而 GA-Mf 导致细胞周期停滞在 G1 期。与 GA-S 相比，GA-Mf 更能增加早期和晚期凋亡细胞的数量。用每种异构体处理 HeLa 细胞会降低线粒体膜电位，并导致细胞色素 c 从线粒体释放到细胞质中。此外，还观察到 caspase-3 和 caspase-9 活性的刺激。GA 处理的 HeLa 细胞中的 Bax/Bcl-2 比值也增加。结果表明，两种异构体 GA-Mf 和 GA-S 通过线粒体介导的途径诱导人 HeLa 细胞凋亡，但它们具有不同的细胞周期停滞特异性。这些发现将有助于从灵芝中开发有用的癌症化学预防化合物。
