Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

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Not AvailableIn the preset study range of variations in physico-chemical, cooking characteristics and antioxidant properties of six pigmented rice (four purple and two red) cultivars from north east India were evaluated. Significant variation (P<0.05) was detected among the cultivars for all the traits evaluated except for volume expansion ratio (VER). All the genotypes had long slender grain. Hulling and milling % for all the genotypes were more than 74 and 61%, respectively. Head rice recovery (HRR) was more than 50% in Manipuriblack, Kalobhat and Assambiroin. The range of amylose content (AC) varied from 2.19 to 24.87% where as Mornodoiga was found with highest AC. All the genotypes except Manipuriblack elongated more than 9mm after cooking. Most of the genotypes were found with soft gel consistency (GC). Similarly, all the genotypes except Assambiroin had water uptake (WU) value £ 100ml/100g rice. The concentration of total anthocyanin content (TAC), total phenolic content (TPC) and antioxidant activity (ABTS) differed significantly among the genotypes with highest concentration of these parameters were observed for the purple grain (Mamihunger) whereas no significant difference between the colour groups (red and purple) was observed for total flavonoid content (TFC), gammaoryzanol and phytic acid content which envisages that value of these parameters depends on genotypes and not on kernel colour. A high correlation of TAC with TPC and ABTS suggest that the major phytochemicals responsible for the tested antioxidant activities are phenolic acids and anthocyanin.Not Availabl