Document Detail


Gallic acid induces apoptosis in A375.S2 human melanoma cells through caspase-dependent and -independent pathways.
MedLine Citation:
PMID:  20596665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The natural antioxidant gallic acid (GA) has demonstrated a significant inhibition of cell proliferation and induction of apoptosis in a series of cancer cell lines. However, there is no available information to show whether GA induces apoptosis in human skin cancer cells. In the present study, we report GA-induced apoptosis in A375.S2 human melanoma cells. GA affected morphological changes, decreased the percentage of viable cells and induced apoptosis in A375.S2 cells in a dose- and time-dependent manner. Observation of the molecular mechanism of apoptosis in A375.S2 cells showed that GA up-regulated the proapoptotic proteins such as Bax, and induced caspase cascade activity, but down-regulated antiapoptotic proteins such as Bcl-2. GA induced reactive oxygen species (ROS) and intracellular Ca2+ productions and decreased the level of mitochondrial membrane potential (DeltaPsim) in A375.S2 cells in a time-dependent manner. GA triggered cytosolic release of apoptotic molecules, cytochrome c, promoted activation of caspase-9 and caspase-3, and ultimately apoptotic cell death. In addition, GA also promoted cytosolic release of apoptosis-inducing factor (AIF) and endonuclease G (Endo G). Therefore, GA may also induce apoptosis through a caspase-independent pathway. Our results suggest that GA might be a potential anticancer compound; however, in depth in vivo studies are needed to elucidate the exact mechanism.
Authors:
Chyi Lo; Tung-Yuan Lai; Jen-Hung Yang; Jai-Sing Yang; Yi-Shih Ma; Shu-Wen Weng; Ya-Yin Chen; Jaung-Geng Lin; Jing-Gung Chung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  377-85     Citation Subset:  IM    
Affiliation:
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / metabolism
Calcium / metabolism
Caspases / metabolism,  physiology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cytochromes c / metabolism
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Gallic Acid / pharmacology*
Humans
Melanoma / metabolism,  pathology*
Membrane Potential, Mitochondrial / drug effects
Models, Biological
Protein Transport / drug effects
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/Reactive Oxygen Species; 149-91-7/Gallic Acid; 7440-70-2/Calcium; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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


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