1.Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells.
Seçme M1, Eroğlu C2, Dodurga Y3, Bağcı G1. Gene. 2016 Jul 1;585(1):93-9. doi: 10.1016/j.gene.2016.03.038. Epub 2016 Mar 24.
Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively.
2.The effect of oleuropein from olive leaf (Olea europaea) extract on Ca(2+) homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells.
Cheng JS1, Chou CT2, Liu YY3, Sun WC4, Shieh P5, Kuo DH5, Kuo CC6, Jan CR7, Liang WZ8. Food Chem Toxicol. 2016 May;91:151-66. doi: 10.1016/j.fct.2016.03.015. Epub 2016 Mar 23.
Oleuropein, a phenolic compound found in the olive leaf (Olea europaea), has been shown to have biological activities in different models. However, the effects of oleuropein on Ca(2+) homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in liver cells have not been analyzed. Oleuropein induced [Ca(2+)]i rises only in HepG2 cells but not in AML12, HA22T or HA59T cells due to the different status of 3-hydroxy-3-methylglutaryl-CoA reductase expression. In HepG2 cells, this Ca(2+) signaling response was reduced by removing extracellular Ca(2+), and was inhibited by the store-operated Ca(2+) channel blockers 2-APB and SKF96365. In Ca(2+)-free medium, pretreatment with the ER Ca(2+) pump inhibitor thapsigargin abolished oleuropein-induced [Ca(2+)]i rises. Oleuropein induced cell cycle arrest which was associated with the regulation of p53, p21, CDK1 and cyclin B1 levels. Furthermore, oleuropein elevated intracellular ROS levels but reduced GSH levels.
3.The polyphenol Oleuropein aglycone hinders the growth of toxic transthyretin amyloid assemblies.
Leri M1, Nosi D2, Natalello A3, Porcari R4, Ramazzotti M5, Chiti F6, Bellotti V7, Doglia SM8, Stefani M9, Bucciantini M10. J Nutr Biochem. 2016 Apr;30:153-66. doi: 10.1016/j.jnutbio.2015.12.009. Epub 2016 Jan 12.
Transthyretin (TTR) is involved in a subset of familial or sporadic amyloid diseases including senile systemic amyloidosis (SSA), familial amyloid polyneuropathy and cardiomyopathy (FAP/FAC) for which no effective therapy has been found yet. These conditions are characterized by extracellular deposits primarily found in the heart parenchyma and in peripheral nerves whose main component are amyloid fibrils, presently considered the main culprits of cell sufferance. The latter are polymeric assemblies grown from misfolded TTR, either wt or carrying one out of many identified mutations. The recent introduction in the clinical practice of synthetic TTR-stabilizing molecules that reduce protein aggregation provides the rationale to search natural effective molecules able to interfere with TTR amyloid aggregation by hindering the appearance of toxic species or by favoring the growth of harmless aggregates. Here we carried out an in depth biophysical and morphological study on the molecular features of the aggregation of wt- and L55P-TTR involved in SSA or FAP/FAC, respectively, and on the interference with fibril aggregation, stability and toxicity to cardiac HL-1 cells to demonstrate the ability of Oleuropein aglycone (OleA), the main phenolic component of the extra virgin olive oil.
4.Oleuropein aglycone and polyphenols from olive mill wastewater ameliorate cognitive deficits and neuropathology.
Pantano D1, Luccarini I1, Nardiello P1, Servili M2, Stefani M3, Casamenti F1. Br J Clin Pharmacol. 2016 Apr 30. doi: 10.1111/bcp.12993. [Epub ahead of print]
AIM: In the TgCRND8 (Tg) mice we checked the dose-response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg/kg of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg/kg of diet) previously investigated.