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Blood, 15 May 2008, Vol. 111, No. 10, pp. 4880-4891. Prepublished online as a Blood First Edition Paper on March 18, 2008; DOI 10.1182/blood-2007-10-117994. This Article Full Text (PDF) All Versions of this Article: blood-2007-10-117994v1 111/10/4880    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Sung, B. Articles by Aggarwal, B. B PubMed PubMed Citation Articles by Sung, B. Articles by Aggarwal, B. B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 12, 2007 Accepted March 13, 2008 Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of NF-B-regulated gene products involved in cell survival, proliferation, invasion and inflammation through inhibition of IB kinase, leading to potentiation of apoptosis Bokyung Sung, Manoj K Pandey, Kwang Seok Ahn, Tingfang Yi, Madan M Chaturvedi, Mingyao Liu, and Bharat B Aggarwal* Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States Institute of Bioscience and Technology, Department of Molecular and Cellular Medicine, Texas A&M University System HSC, Houston, TX, United States * Corresponding author; email: aggarwal{at}mdanderson.org. Anacardic acid (6-pentadecylsalicylic acid) is derived from traditional medicinal plants such as cashew nuts and has been linked to anticancer, anti-inflammatory, and radiosensitization activities through a mechanism that is not yet fully understood. Because of the role of NF-B activation in these cellular responses, we postulated that anacardic acid might interfere this pathway. We found that this salicylic acid potentiated the apoptosis induced by cytokine and chemotherapeutic agents, which correlated with the downregulation of various gene products that mediate proliferation (cyclin D1 and COX-2), survival (Bcl-2, Bcl-xL, cFLIP, cIAP-1, and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF), all known to be regulated by the NF-B. We found that anacardic acid inhibited both inducible and constitutive NF-B activation; suppressed the activation of IB kinase that led to abrogation of phosphorylation and degradation of IB; acetylation and nuclear translocation of p65; and NF-B-dependent reporter gene expression. Downregulation of the p300 HAT gene by RNA interference abrogated the effect of anacardic acid on NF-B suppression, suggesting the critical role of this enzyme. Overall, our results demonstrate a novel role for anacardic acid in potentially preventing or treating cancer through modulation of NF-B signaling pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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