Antioxidant and antigrowth action of peracetylated oleuropein in thyroid cancer cells

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.

Oleuropein Induced Apoptosis in HeLa Cells via a Mitochondrial Apoptotic Cascade Associated With Activation of the c-Jun NH2-Terminal Kinase

“…6B), suggesting that oleuropein-induced HeLa cell death is dependent on the JNK signaling pathway that plays a critical role in inducing apoptosis. However, other reports suggest that oleuropein-induced apoptotic cell death is associated with NF-kB (58), HIF-1a (62), PI3K-Akt (17,63), ERK (64,65). Such differential effects observed from one study to another could reflect cell type or treatment specificity.…”

Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line

“…Andreadou et al reported that oleuropein is involved in cardiomyocyte metabolism through the activation of AMP-activated protein kinase α (AMPK) and suppression of inducible nitric oxide synthases (iNOS) (11). It has recently been reported that oleuropein may have therapeutic potential in a number of types of cancer, including breast cancer (12), thyroid cancer (13) and colorectal cancer (14), via inhibition of cell growth induction of apoptosis. However, to date the effects of oleuropein on liver cancer remain largely unknown.…”

Safety evaluation of subchronic oral administration of Oleuropein and its semisynthetic peracetylated derivative

“…Recent reports [24] have suggested the potential improvements concerning the OLE effect by protecting the molecule through its peracetylation. In previous studies, we have shown that Ac-OLE has a stronger anti-proliferative effect than OLE in the experimental models of tumor cells in vitro [8,9] . Also in a very recent study, we demonstrate the beneficial effects of Ac-OLE at the same dose (20 mg/kg/day) in the prevention of hepatic steatosis, hyperinsulinemia and weight gain in mice fed with high fat cafeteria diet [25] .…”

“…Due to their health benefits, oleuropein, oleuropein derivatives, and seco-phenolic compounds are all considered to be important elements that make extra virgin olive oil a staple part of the Mediterranean diet. Also, the compounds include the ability to scavenge reactive oxygen species (ROS) [5][6][7] , to inhibit the proliferation of several tumor cell lines [5,[8][9][10][11] , and also to protect against cardiovascular diseases [3,[12][13][14][15] and metabolic disorders as Diabetes mellitus [16][17][18][19] . In addition, they are effective in experimental models of age-related disorders, such as neurodegenerative diseases [14,20,21] .…”

“…By using an innovative extractive method that employs renewable sources of primary matter and adopts sustainable synthetic strategies, we obtained OLE and some acetylated derivatives in good yields and very mild conditions [22,23] ; interestingly, the latter compounds have shown an improved capacity to permeate the molecular membrane, in addition to their 'drug likeness' [22] . Moreover, we have recently demonstrated that peracetylated oleuropein (Ac-OLE) possesses in vitro an antioxidant and a growth-inhibitory activity that is even stronger than OLE when acting against both breast and thyroid cancer cell lines [8,9] . While the absence of toxicity of oleuropein is well established [1,5,11] , very little is known about the in vivo effects of its peracetylated derivative.…”