Gliotoxin Isolated from Marine Fungus Aspergillus sp.Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

Marine Drugs

Zhong-Ji Qian¹  Won-Kyo Jung²  Van-Tinh Nguyen²  Jae-Young Je³  You-Jin Jeon⁴  Il-Whan Choi⁵  Won Sun Park⁶  Soo-Jin Heo⁷  Jung Suck Lee⁸  Kil-Nam Kim⁹  Yong-Xin Li^1,10 

[1] College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China;Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea;Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 550-749, Korea;Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea;Department of Microbiology, College of Medicine, Inje University, Busan 608-737, Korea;Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, Korea;Global Bioresources Research Center, Korea Institute of Ocean Science & Technology, Ansan426-744, Korea;Industry-Academic Cooperation Foundation, Jeju National University, Jeju 690-756, Korea;Marine Bio Research Team, Korea Basic Science Institute (KBSI), Jeju 690-140, Korea;Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Korea;

关键词: apoptosis;    Aspergillus sp.;    gliotoxin;    human cervical cancer cells;    human chondrosarcoma cells;   

DOI  :  10.3390/md12010069

来源: DOAJ

【 摘 要 】

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 ofBcl-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.

【 授权许可】

Unknown