Document Detail


Kahweol blocks STAT3 phosphorylation and induces apoptosis in human lung adenocarcinoma A549 cells.
MedLine Citation:
PMID:  19429240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Kahweol, the coffee-specific diterpene, has been reported to have anti-carcinogenic properties. Animal data support such a chemopreventive effect of coffee. However, the precise underlying protective mechanisms are poorly understood. In this study, the apoptotic effect of kahweol in human lung adenocarcinoma A549 cells was investigated. In cell viability assays and cell proliferation assays, kahweol exhibited anti-proliferative and pro-apoptotic effects on A549 cells in a time- and dose-dependent manner. Kahweol considerably inhibited the expression of Bcl-2 but increased that of Bax; it also stimulated the cleavage of caspase-3 and PARP (poly ADP-ribose polymerase). In addition, kahweol-induced apoptosis was confirmed by TUNEL assays. Furthermore, kahweol inhibited dose-dependent phosphorylation of signal transducer and activator of transcription 3 (STAT3). An overexpression in STAT3 led to resistance to kahweol-induced apoptosis, suggesting that STAT3 was a critical target of kahweol. These findings suggest that kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway.
Authors:
Hyung Gyun Kim; Yong Pil Hwang; Hye Gwang Jeong
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-24
Journal Detail:
Title:  Toxicology letters     Volume:  187     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-05-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  28-34     Citation Subset:  IM    
Affiliation:
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / metabolism,  pathology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Down-Regulation / drug effects
Drug Screening Assays, Antitumor
Humans
In Situ Nick-End Labeling
Lung Neoplasms / metabolism,  pathology*
Mitochondria / drug effects
Phosphorylation / drug effects
Proto-Oncogene Proteins c-bcl-2 / metabolism
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Time Factors
Tumor Cells, Cultured
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BAX protein, human; 0/Diterpenes; 0/Proto-Oncogene Proteins c-bcl-2; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/bcl-2-Associated X Protein; 6894-43-5/kahweol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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