PMID- 24368570
OWN - NLM
STAT- MEDLINE
DCOM- 20140915
LR  - 20220409
IS  - 1660-3397 (Electronic)
IS  - 1660-3397 (Linking)
VI  - 12
IP  - 1
DP  - 2013 Dec 24
TI  - Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human 
      cervical cancer and chondrosarcoma cells.
PG  - 69-87
LID - 10.3390/md12010069 [doi]
AB  - 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.
FAU - Nguyen, Van-Tinh
AU  - Nguyen VT
FAU - Lee, Jung Suck
AU  - Lee JS
FAU - Qian, Zhong-Ji
AU  - Qian ZJ
FAU - Li, Yong-Xin
AU  - Li YX
FAU - Kim, Kil-Nam
AU  - Kim KN
FAU - Heo, Soo-Jin
AU  - Heo SJ
FAU - Jeon, You-Jin
AU  - Jeon YJ
FAU - Park, Won Sun
AU  - Park WS
FAU - Choi, Il-Whan
AU  - Choi IW
FAU - Je, Jae-Young
AU  - Je JY
AD  - Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical 
      Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea. 
      jjy1915@jnu.ac.kr.
FAU - Jung, Won-Kyo
AU  - Jung WK
AD  - Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical 
      Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea. 
      wkjung@pknu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131224
PL  - Switzerland
TA  - Mar Drugs
JT  - Marine drugs
JID - 101213729
RN  - 0 (Annexin A5)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Biological Products)
RN  - 0 (Coloring Agents)
RN  - 0 (Indoles)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 36015-30-2 (Propidium)
RN  - 47165-04-8 (DAPI)
RN  - 67-99-2 (Gliotoxin)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Annexin A5
MH  - *Antineoplastic Agents
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/antagonists & inhibitors/biosynthesis
MH  - Aspergillus/*chemistry
MH  - Biological Products/*pharmacology
MH  - Caspases/biosynthesis
MH  - Cell Line, Tumor
MH  - Chondrosarcoma/drug therapy
MH  - Coloring Agents
MH  - DNA Fragmentation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gliotoxin/*isolation & purification/*pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Indoles
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Phosphatidylserines/metabolism
MH  - Propidium
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis
MH  - Uterine Cervical Neoplasms/drug therapy
PMC - PMC3917261
EDAT- 2013/12/26 06:00
MHDA- 2014/09/16 06:00
PMCR- 2014/01/01
CRDT- 2013/12/26 06:00
PHST- 2013/10/08 00:00 [received]
PHST- 2013/12/09 00:00 [revised]
PHST- 2013/12/11 00:00 [accepted]
PHST- 2013/12/26 06:00 [entrez]
PHST- 2013/12/26 06:00 [pubmed]
PHST- 2014/09/16 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - md12010069 [pii]
AID - marinedrugs-12-00069 [pii]
AID - 10.3390/md12010069 [doi]
PST - epublish
SO  - Mar Drugs. 2013 Dec 24;12(1):69-87. doi: 10.3390/md12010069.