title: Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human cervical cancer and chondrosarcoma cells.
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.
authors.forename: Van-Tinh
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Jung Suck
authors.initials: JS
authors.lastname: Lee
authors.forename: Zhong-Ji
authors.initials: ZJ
authors.lastname: Qian
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Li
authors.forename: Kil-Nam
authors.initials: KN
authors.lastname: Kim
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Heo
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea. jjy1915@jnu.ac.kr.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Je
authors.affiliation: Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea. wkjung@pknu.ac.kr.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
mesh_terms: D017304:Annexin A5; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D001230:Aspergillus / Q000737:chemistry*; D001688:Biological Products / Q000494:pharmacology*; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy; D004396:Coloring Agents; D053938:DNA Fragmentation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005912:Gliotoxin / Q000302:isolation & purification* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007211:Indoles; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D011419:Propidium; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001688:Biological Products; D004396:Coloring Agents; D007211:Indoles; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D011419:Propidium; C007293:DAPI; D005912:Gliotoxin; D020169:Caspases