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Anacardic Acid (6-Pentadecylsalicylic Acid) Inhibits Tumor Angiogenesis by Targeting Src/FAK/Rho GTPases Signaling Pathway.
MedLine Citation:
PMID:  21828260     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Anacardic acid (6-pentadecylsalicylic acid), a natural inhibitor of histone acetyltransferase from Amphipterygium adstringens, has been implicated in anti-inflammatory, anticancer, antioxidative and antimicrobial functions. However, whether this salicylic acid could block angiogenesis has not been elucidated to date. Here, we postulate that anacardic acid affects multiple steps of tumor angiogenesis to contribute to its tumor inhibition. In this study, we found that vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, adhesion and capillary-like structure formation of primary cultured human umbilical vascular endothelial cells (HUVECs) could all be significantly suppressed by anacardic acid in vitro, without detectable cellular toxicity. Furthermore, anacardic acid effectively inhibited the vascular development in chick embryo chorioallantoic membrane ex vivo (n=10) and VEGF-triggered corneal neovascularization in vivo (n=10). Mechanistic study revealed that anacardic acid blocked activities of Src and FAK kinases in concentration- and time-dependent manners in HUVECs, resulting in activation of RhoA-GTPase and inactivation of Rac1- and Cdc42-GTPases. Notably, when subcutaneously administrated with anacardic acid (2 mg/kg/d) to mice bearing human prostate tumor xenografts (n=6~7), the volume and weight of solid tumors were significantly retarded. Src, Ki-67 and CD31 imunohistochemistry further revealed that Src protein expression, tumor cell proliferation and microvessel density could be remarkably suppressed by anacardic acid. Taken together, our findings demonstrate for the first time that anacardic acid functions as a potent tumor angiogenesis inhibitor by targeting Src/FAK/Rho GTPases signaling pathway, leading to significant suppression of prostate tumor growth.
Authors:
Yuanyuan Wu; Lijun He; Li Zhang; Jing Chen; Zhengfang Yi; Jian Zhang; Mingyao Liu; Xiufeng Pang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-9
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  -     ISSN:  1521-0103     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Institute of Biomedical Sciences and School of Life Sciences, East China Normal University;
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