Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human cervical cancer and chondrosarcoma cells.
Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human cervical cancer and chondrosarcoma cells.
复制标题
DOI：
10.3390/md12010069
复制
发表时间：
2013-12-24
期刊：
影响因子：
5.4
通讯作者：
Jung WK
中科院分区：
文献类型：
--
作者：
Nguyen VT;Lee JS;Qian ZJ;Li YX;Kim KN;Heo SJ;Jeon YJ;Park WS;Choi IW;Je JY;Jung WK
胶质毒素是海洋真菌曲霉（Aspergillus sp.）产生的次生代谢产物，具有多种生物活性，包括抗癌活性。然而，胶质毒素诱导的人宫颈癌（Hela）和人软骨肉瘤（SW1353）细胞毒性的机制尚不清楚。在本研究中，我们重点研究了胶质毒素诱导对细胞凋亡的影响，以及激活caspase家族酶在细胞中的表达。通过DAPI和膜联蛋白V/碘化丙啶（PI）双染色检测凋亡细胞水平。Western blot检测Hela和SW1353细胞中凋亡蛋白Bcl-2和caspase家族的表达。我们的研究结果表明，胶质毒素处理抑制了细胞的增殖，并引起了明显的形态学改变。胶质毒素诱导的细胞凋亡进一步通过DNA断裂、染色质凝聚和线粒体膜电位破坏得到证实。胶质毒素诱导caspase-3、caspase-8和caspase-9的激活，下调Bcl-2，上调Bax和细胞色素（cyt - c）的释放，证明了胶质毒素对细胞凋亡的活性。这些结果表明，从海洋真菌Aspergillus sp.中分离的胶质毒素通过线粒体途径诱导Hela和SW1353细胞凋亡，随后发生下游事件导致细胞死亡的凋亡模式。
Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death.
登录
查看更多内容
影响因子：
7.9
作者：
Li, Zhi-Bo;Wang, Jing-Yun;Bao, Yong-Ming
通讯作者：
Bao, Yong-Ming
Aspergilones A 和 B，两种苄基氮杂酮，具有前所未有的碳骨架，来自柳珊瑚衍生真菌 Aspergillus sp。
影响因子：
2.7
作者：
Shao, Chang-Lun;Wang, Chang-Yun;Lin, Yong-Cheng
通讯作者：
Lin, Yong-Cheng
影响因子：
3.2
作者：
Park, Cheol;Shin, Hee Jae;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
4.2
作者：
Li, Xihai;Yei, Hongzhi;Liu, Xianxiang
通讯作者：
Liu, Xianxiang
影响因子：
3.5
作者：
Lee, Dong-Sung;Jeong, Gil-Saeng;Kim, Youn-Chul
通讯作者：
Kim, Youn-Chul