Plant Polyphenols and Oxidative Metabolites of the Herbal Alkenylbenzene Methyleugenol Suppress Histone Deacetylase Activity in Human Colon Carcinoma Cells
Evidence has been provided that diet and environmental factors directly influence epigenetic mechanisms associated with cancer development in humans. The inhibition of histone deacetylase (HDAC) activity and the disruption of the HDAC complex have been recognized as a potent strategy for cancer therapy and chemoprevention. In the present study, we investigated whether selected plant constituents affect HDAC activity or HDAC1 protein status in the human colon carcinoma cell line HT29. The polyphenols (？)-epigallocatechin-3-gallate (EGCG) and genistein (GEN) as well as two oxidative methyleugenol (ME) metabolites were shown to inhibit HDAC activity in intact HT29 cells. Concomitantly, a significant decrease of the HDAC1 protein level was observed after incubation with EGCG and GEN, whereas the investigated ME metabolites did not affect HDAC1 protein status. In conclusion, dietary compounds were found to possess promising HDAC-inhibitory properties, contributing to epigenetic alterations in colon tumor cells, which should be taken into account in further risk/benefit assessments of polyphenols and alkenylbenzenes. 1. Introduction Cancer is one of the most causes of death in industrial countries. Especially the genesis of tumors of the gastrointestinal tract seems to depend on genetic predisposition, environmental factors, and diet [1]. Evidence has been provided that these factors directly influence epigenetic mechanisms associated with cancer development in humans. Epigenetic mechanisms comprise modulation in DNA methylation, histone modification, and noncoding RNA [2]. DNA methylation/demethylation and histone modifications are controlled by specific enzymes, such as DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC) [3, 4]. One of the major posttranslational epigenetic regulations of gene expression is the modulation of histones via acetylation and deacetylation [5]. HDACs belong to the group of zinc-binding metalloenzymes catalyzing the elimination of acetyl groups from histone tails. Deacetylation results in the tighter wrapping of DNA around the histone core leading to chromatin condensation. Based on this cellular event the accessibility of transcription factors and gene expression is decreased. HDACs are involved in several cellular regulation processes such as transcription, cell cycle progressing, gene silencing, cell differentiation, DNA-replication and DNA-damage response [5, 6]. Up to now, 18 human HDAC enzymes are characterized and classified into four classes: class I HDACs share sequence similarity
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