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Mar. Drugs 2014, 12(1), 69-87; doi:10.3390/md12010069
Article

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

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1 Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea 2 Industry-Academic Cooperation Foundation, Jeju National University, Jeju 690-756, Korea 3 College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China 4 Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Korea 5 Marine Bio Research Team, Korea Basic Science Institute (KBSI), Jeju 690-140, Korea 6 Global Bioresources Research Center, Korea Institute of Ocean Science & Technology, Ansan 426-744, Korea 7 Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea 8 Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, Korea 9 Department of Microbiology, College of Medicine, Inje University, Busan 608-737, Korea 10 Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 550-749, Korea These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 8 October 2013 / Revised: 9 December 2013 / Accepted: 11 December 2013 / Published: 24 December 2013
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Abstract

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.
Keywords: apoptosis; Aspergillus sp.; gliotoxin; human cervical cancer cells; human chondrosarcoma cells apoptosis; Aspergillus sp.; gliotoxin; human cervical cancer cells; human chondrosarcoma cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Nguyen, V.-T.; Lee, J.S.; Qian, Z.-J.; Li, Y.-X.; Kim, K.-N.; Heo, S.-J.; Jeon, Y.-J.; Park, W.S.; Choi, I.-W.; Je, J.-Y.; Jung, W.-K. Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells. Mar. Drugs 2014, 12, 69-87.

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