Oleuropein, the main phenolic compound in virgin olive oil, and several of its derivatives such as oleuropein aglycone, hydroxytyrosol, and their respective acetylated lipophilic forms were obtained by simple and environmentally friendly semisynthetic protocols. The same molecules were then tested in vitro and in vivo, comparing their intriguing anti-COX-1 and anti-COX-2 properties to those of well-known anti-inflammatory drugs such as ibuprofen and celecoxib. Finally, molecular modeling experiments displaying the most probable binding modes within the classical binding clefts of the enzymes suggest the heme moiety as a potential alternative target.

The transformation of furfural into functionalized cyclopentenone derivatives is a smart process to advance the sustainable synthesis of important chemicals from biomass.

No abstract

No abstract

The olive tree phenolic component oleuropein (OLE) and its derivatives have shown many biological properties, thus representing promising novel therapeutics for the treatment of several diseases, including neoplasia. In this study, we evaluated the activities of OLE and its peracetylated derivative (peracetylated oleuropein, Ac-OLE) against two thyroid tumor cell lines that host genotypic alterations detected in human papillary thyroid cancer. TPC-1 and BCPAP cells were treated with OLE and Ac-OLE, and the effects on viability were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell counting, and trypan blue exclusion assays. Antioxidant effects were analyzed by measuring the reactive oxygen species (ROS) in basal conditions and after treatment with hydrogen peroxide (H2O2). Activity of MAP kinase and PI3K-Akt signaling pathways was evaluated by examining the levels of phosphorylated ERK and Akt by western blot. We found that OLE significantly inhibited the proliferation of both cell lines. This effect was paralleled by a reduction of basal phospho-Akt and phospho-ERK levels and H2O2-induced ROS levels. A stronger effect was elicited by Ac-OLE either in inhibiting cell growth or as an antioxidant, in particular on BCPAP cells. Our results demonstrate that OLE and especially Ac-OLE inhibit in vitro thyroid cancer cell proliferation acting on growth-promoting signal pathways, as well as exerting antioxidant effects. Further studies will reveal the potential application as novel targeted therapeutics in thyroid cancer.

No abstract

No abstract

Olive oil contains different biologically active polyphenols, among which oleacein, the most abundant secoiridoid, has recently emerged for its beneficial properties in various disease contexts. By using in vitro models of human multiple myeloma (MM), we here investigated the anti-tumor potential of oleacein and the underlying bio-molecular sequelae. Within a low micromolar range, oleacein reduced the viability of MM primary samples and cell lines even in the presence of bone marrow stromal cells (BMSCs), while sparing healthy peripheral blood mononuclear cells. We also demonstrated that oleacein inhibited MM cell clonogenicity, prompted cell cycle blockade and triggered apoptosis. We evaluated the epigenetic impact of oleacein on MM cells, and observed dose-dependent accumulation of both acetylated histones and α-tubulin, along with down-regulation of several class I/II histone deacetylases (HDACs) both at the mRNA and protein level, providing evidence of the HDAC inhibitory activity of this compound; conversely, no effect on global DNA methylation was found. Mechanistically, HDACs inhibition by oleacein was associated with down-regulation of Sp1, the major transactivator of HDACs promoter, via Caspase 8 activation. Of potential translational significance, oleacein synergistically enhanced the in vitro anti-MM activity of the proteasome inhibitor carfilzomib. Altogether, these results indicate that oleacein is endowed with HDAC inhibitory properties, which associate with significant anti-MM activity both as single agent or in combination with carfilzomib. These findings may pave the way to novel potential anti-MM epi-therapeutic approaches based on natural agents.