Nutrition, Diet and Cancer by Sharmila Shankar & Rakesh K. Srivastava

Author:Sharmila Shankar & Rakesh K. Srivastava
Language: eng
Format: epub
Publisher: Springer Netherlands, Dordrecht

Anacardic Acid and Garcinol

Anacardic acid (AA) is the most active principle present in cashew nuts, and has been shown to be a potent and specific HAT inhibitor. HAT inhibitory activity of AA associates with the down-regulation of p300, PCAF and Tip60 HAT factors (Balasubramanyam et al. 2003; Sun et al. 2006). AA exerts its effect by inhibiting HAT-dependent transcription, which strongly correlates with simultaneous histone H3 and/or H4 hypoacetylation in HeLa and MCF7 cancer cells (Balasubramanyam et al. 2003; Eliseeva et al. 2007). In fact knowledge gained from the HAT inhibitory activity of AA has paved path for the development of new synthetic HAT inhibitors and activators (Chandregowda et al. 2009; Sbardella et al. 2008; Souto et al. 2008). Only very few studies have evaluated the molecular biological relevance of AA-related HAT inhibitory activity. Sung et al. showed that AA inhibits both inducible and constitutive NF-κB activation, and suppresses activation of IκBα kinase which leads to abrogation of its phosphorylation and eventual degradation in multiple cancer cells (Sung et al. 2008). In addition, using human dermal fibroblasts it was demonstrated that AA effectively inhibits UV-induced cancer formation and premature skin aging by reducing UV-enhanced levels of c-H2AX, p53, and acetylation of H3 (Kim et al. 2009).

Garcinol is a cytotoxic poly-isoprenylated benzophenone derivative from garcinia fruit rinds. Similar to anacardic acid, garcinol is a potent inhibitor of different HATs, such as, p300 and PCAF (Balasubramanyam et al. 2004; Chandregowda et al. 2009; Mai et al. 2006). A recent mechanistic work using fluorescence, docking and mutational studies, has revealed that garcinol induces alteration in the secondary structure of the HAT proteins (Arif et al. 2007). Analogous to curcumin and AA, garcinol also possesses significant histone H3 and H4 deacetylating activities (Arif et al. 2007). In addition, garcinol also has the ability to inhibit auto-acetylation of p300, which is one of the key regulatory mechanisms for its catalytic activity in HeLa core histones (Arif et al. 2007). Although none of the studies have specifically evaluated the effects of garcinol on gene-specific histone modifications, existing data indicates that garcinol and/or its synthetic derivate LTK14, down-regulates the expression of multiple genes in cervical cancer cells and T-lymphocytes (Mantelingu et al. 2007).

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