Two Trichothecene Mycotoxins from Myrothecium roridum Induce Apoptosis of HepG-2 Cells via Caspase Activation and Disruption of Mitochondrial Membrane Potential.
Two Trichothecene Mycotoxins from Myrothecium roridum Induce Apoptosis of HepG-2 Cells via Caspase Activation and Disruption of Mitochondrial Membrane Potential.
复制标题
来自红色漆斑菌的两种单端孢菌素真菌毒素通过 Caspase 激活和线粒体膜电位破坏诱导 HepG-2 细胞凋亡
DOI：
10.3390/molecules21060781
复制
发表时间：
2016-06-17
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Ye W;Chen Y;Li H;Zhang W;Liu H;Sun Z;Liu T;Li S
单端孢霉烯真菌毒素是由多种植物病原真菌产生的一类倍半萜类化合物。本研究从药用植物广藿香内生真菌Myrothecium roridum中分离得到两种新的胞苷类毒素，即一种新的细胞毒性epiroridin酸和一种已知的胞苷类毒素mytoxin B。通过细胞形态学观察、DNA片段化检测和流式细胞术检测，证实两种地衣芽孢杆菌毒素均能诱导HepG-2细胞凋亡。采用定量真实的时间聚合酶链反应、蛋白质印迹法和线粒体膜电位检测等方法研究了两种真菌毒素的细胞毒作用机制。结果表明，两种青霉烯类真菌毒素通过激活caspase-9和caspase-3，上调bax基因表达，下调bcl-2基因表达，破坏HepG-2细胞线粒体膜电位，诱导HepG-2细胞凋亡。本研究首次报道了产自M.罗里丹本研究为进一步开发减毒抗肝癌药物提供了新的思路。
Trichothecene mycotoxins are a type of sesquiterpenoid produced by various kinds of plantpathogenic fungi. In this study, two trichothecene toxins, namely, a novel cytotoxic epiroridin acid and a known trichothecene, mytoxin B, were isolated from the endophytic fungus Myrothecium roridum derived from the medicinal plant Pogostemon cablin. The two trichothecene mytoxins were confirmed to induce the apoptosis of HepG-2 cells by cytomorphology inspection, DNA fragmentation detection, and flow cytometry assay. The cytotoxic mechanisms of the two mycotoxins were investigated by quantitative real time polymerase chain reaction, western blot, and detection of mitochondrial membrane potential. The results showed that the two trichothecene mycotoxins induced the apoptosis of cancer cell HepG-2 via activation of caspase-9 and caspase-3, up-regulation of bax gene expression, down-regulation of bcl-2 gene expression, and disruption of the mitochondrial membrane potential of the HepG-2 cell. This study is the first to report on the cytotoxic mechanism of trichothecene mycotoxins from M. roridum. This study provides new clues for the development of attenuated trichothecene toxins in future treatment of liver cancer.
登录
查看更多内容
影响因子：
4.2
作者：
Hsieh PF;Chiu HC;Chen KC;Chang CH;Chou EC
通讯作者：
Chou EC
影响因子：
11.2
作者：
Veiseh, Mandana;Gabikian, Patrik;Olson, James M.
通讯作者：
Olson, James M.
影响因子：
4.3
作者：
Frankic, T.;Pajk, T.;Salobir, J.
通讯作者：
Salobir, J.
影响因子：
6.6
作者：
Thakur, Mayank;Mergel, Katharina;Fuchs, Hendrik
通讯作者：
Fuchs, Hendrik
DOI：
10.1016/s2221-1691(13)60042-8
发表时间：
2013-02-01
影响因子：
1.7
作者：
Vyas, Vivek Kumar;Brahmbhatt, Keyur;Parmar, Utsav
通讯作者：
Parmar, Utsav