In this study, we examine the effect of extra virgin olive oil phenolic compounds on homocysteine-induced endothelial dysfunction and whether the protective effects are related to their different scavenging activities. Structurally related compounds have been assayed for their ability to reduce homocysteine-induced monocyte adhesion as well as the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) in EA.hy.926 cells. As well-known, among the selected phenolic compounds, hydroxytyrosol, homovanillyl alcohol, and the hydroxycinnamic acid derivatives caffeic and ferulic acid display high scavenging activities, while tyrosol and p-coumaric acid are poorly active. All of the tested compounds, approaching potential in vivo concentrations, significantly reduce homocysteine-induced cell adhesion and ICAM-1 expression. Interestingly, we report the first evidence that monophenols tyrosol and p-coumaric acid are selectively protective only in homocysteine-activated cells, while they are ineffective in reducing ICAM-1 expression induced by TNFalpha. Finally, we report the synergistic effect of o-diphenolic and monophenolic compounds.

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In a previous work, taking advantage of the gene-array screening technology, we analysed the effects of histone deacetylase (HDAC) inhibitor sodium butyrate (NaBt), on gene transcription in HT29 human adenocarcinoma cell line. In this study, we focused our attention on p55CDC/Cdc20 gene, whose expression was dramatically reduced by NaBt treatment. Mammalian p55CDC/Cdc20 interacts with the anaphase promoting complex/cyclosome (APC/C), and is involved in regulating anaphase onset and late mitotic events. Using NaBt and trichostatin A (TSA), a member of the HDAC inhibitor family, we showed that both HDAC inhibitors totally downregulated p55CDC/Cdc20 transcription and expression. Cell cycle analysis demonstrated that NaBt arrested HT29 cells in G0/G1 phase, while TSA caused a double block in G0/G1 and G2/M phases. Moreover, p55CDC/Cdc20 showed maximal expression in S and G2/M phases of HT29 cell division cycle. Based on this evidence, and by means of specific cell cycle modulators, such as nocodazole and hydroxyurea, we demonstrated that both TSA and NaBt were responsible for loss of p55CDC/Cdc20 expression, but with different mechanisms of action. Taken together, these results suggest that targeting molecules involved in spindle mitotic checkpoint, such as p55CDC/Cdc20, might account for the high cytotoxicity of HDAC inhibitors versus malignant cells.