Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-κB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-KBa kinase, leading to potentiation of apoptosis

Bokyung Sung, Manoj K. Pandey, Kwang Seok Ann, Tingfang Yi, Madan M. Chaturvedi, Mingyao Liu, Bharat B. Aggarwal

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216 Scopus citations

Abstract

Anacardic acid (6-pentadecylsalicylic acid) is derived from traditional medicinal plants, such as cashew nuts, and has been linked to anticancer, anti-inflammatory, and radio- sensitization activities through a mechanism that is not yet fully understood. Because of the role of nuclear factor-κB (NF-κB) activation in these cellular responses, we postulated that anacardic acid might interfere with this pathway. We found that this salicylic acid potentiated the apoptosis induced by cytokine and chemotherapeutic agents, which correlated with the down- regulation of various gene products that mediate proliferation (cyclin D1 and cyclooxygenase-2), survival (Bcl-2, Bcl-xL, cFLIP, clAP-1, and survivin), invasion (matrix metalloproteinase-9 and intercellular adhesion molecule-1), and angiogenesis (vascular endothelial growth factor), all known to be regulated by the NF-κB. We found that anacardic acid inhibited both inducible and constitutive NF-κB activation; suppressed the activation of IκBα kinase that led to abrogation of phosphorylation and degradation of IκBα; inhibited acetylation and nuclear translocation of p65; and suppressed NF-κ-B-dependent reporter gene ex-pression. Down-regulation of the p300 histone acetyltransferase gene by RNA interference abrogated the effect of anacardic acid on NF-kB 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-κB signaling pathway.

Original languageEnglish (US)
Pages (from-to)4880-4891
Number of pages12
JournalBlood
Volume111
Issue number10
DOIs
StatePublished - May 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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