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NOVEL AMIDOXIMES THAT INDUCE APOPTOSIS OF COLON CARCINOMA CELLS DECREASE HISTONE ACETYLATION AND INHIBIT p300 IN VITRO
Author(s) -
REDDY SUDHEER REDDY DHANI
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb377
Subject(s) - acetylation , histone , chromatin , histone acetyltransferase , histone acetyltransferases , chemistry , microbiology and biotechnology , histone modifying enzymes , in vitro , histone octamer , biochemistry , apoptosis , histone h4 , dna , histone h2a , biology , nucleosome , gene
The eukaryotic nucleus contains chromatin which consists of DNA wrapped 1.6 times around repetitive units of histone octamer called core particles. The folding and unfolding of chromatin can be regulated by the deacetylation and acetylation of lysine residues on the histones, respectively. Histone acetyltransferases and histone deacetylases are two groups of enzymes that modulate the degree of acetylation of histones, therefore regulating the levels of gene expression. Our project tested the growth inhibition effect of nine novel amidoximes on six malignant cell lines. Four of the compounds showed a specific and significant inhibition of proliferation in several malignant cell lines. DNA fragmentation assay and cleavage of caspase 3 demonstrated that these compounds also induced apoptosis in colon cancer cells. These compounds inhibited the acetylation of specific lysines on core histones in colon cancer cells. In vitro acetylation assays revealed that one of the amidoximes, JJMB9, is an inhibitor of the histone acetyltransferase p300. These results show for the first time to our knowledge, amidoximes that demonstrate HAT inhibition activity and anti‐proliferative effect.