9-Hydroxystearic acid and sulforaphane: two natural HDAC inhibitors with distinct effects on HT29 cells.

Among active compounds introduced with diet or originating from cellular metabolism, 9-hydroxystearic acid 89-HSA) and sulforaphane (SFN) are two promising modulators of cell proliferation and differentiation. 9-HSA is a dietary fatty acid, contained in apple skin, in the cutin of Finnish berries and in the seed oil of sea bucktorn, as well as an endogenous lipoperoxidation product, identifiee in several normal and neoplastic human cell lines. SFN is the major isothiocyanate derived from Brassicaceae, largely studied for its chemiopreventive activity. They both exhibit antiproliferative effects, inducing growth arrest and apoptosis in various cancer cell lines. In particular, their administration to HT29, a human colon adenocarcinoma cell line, causes a proliferative arrest mediated by a direct activation of p21WAF1 gene, bypassing p53. These effects have been found to be related to the inhibition of histone deacetylases (HDACs): despite their different chemical structures, 9-HSA and SFN are both able to directly interact with the catalitic site of HDAC1, leading to a reduced enzymatic activity. In this study we have investigated 9-HSA and SFN effects on core histones acetylation status, and its correlation with HT29 cell growth and differentiation.