Effects Of Oleocanthal Research Articles

Inhibiting effect of oleocanthal on neuroblastoma cancer cell proliferation in culture

ABSTRACTWe investigated the potential anticancer effects of oleocanthal (OC) on neuroblastoma cells. Cells were divided into four groups: group 1, neuroblastoma cells were treated with OC; group 2, neurons that differentiated from neuroblastoma cells were treated with phosphate-buffered saline(PBS); group 3, bone marrow derived neuronal (BMDN) cells that were differentiated from bone marrow derived mesenchymal stem cells (BMSCs) were treated with OC; group 4, BMDN cells that were differentiated from BMSCs were treated with PBS. Groups 2 and 4 were control groups. The effects of OC on cell viability, oxidative stress, neurite inhibition and apoptosis at IC50 dose were investigated using MTT analysis, i-NOS and e-NOS measurement, neurotoxicity screening test (NST) and TUNEL staining, respectively. MTT analysis demonstrated that cells were significantly less viable in group 1 than in group 3. i-NOS and e-NOS staining intensity was significantly greater in group 1 than in group 3. NST revealed that OC inhibited neurite growth in both neuroblastoma and BMND cells; inhibition was significantly less in group 3 than in group 1. Significantly more TUNEL labeled cells were found in group 1 than in group 3. We found that OC prevented growth and proliferation of neuroblastoma cells in culture by increasing oxidative stress and apoptosis. We also found that the cytotoxicity of OC is negligible in BMDN cells.

(−)‑Oleocanthal inhibits proliferation and migration by modulating Ca2+ entry through TRPC6 in breast cancer cells

Triple negative breast cancer is an aggressive type of cancer that does not respond to hormonal therapy and current therapeutic strategies are accompanied by side effects due to cytotoxic actions on normal tissues. Therefore, there is a need for the identification of anti-cancer compounds with negligible effects on non-tumoral cells. Here we show that (−)‑oleocanthal (OLCT), a phenolic compound isolated from olive oil, selectively impairs MDA-MB-231 cell proliferation and viability without affecting the ability of non-tumoral MCF10A cells to proliferate or their viability. Similarly, OLCT selectively impairs the ability of MDA-MB-231 cells to migrate while the ability of MCF10A to migrate was unaffected. The effect of OLCT was not exclusive for triple negative breast cancer cells as we found that OLCT also attenuate cell viability and proliferation of MCF7 cells. Our results indicate that OLCT is unable to induce Ca2+ mobilization in non-tumoral cells. By contrast, OLCT induces Ca2+ entry in MCF7 and MDA-MB-231 cells, which is impaired by TRPC6 expression silencing. We have found that MDA-MB-231 and MCF7 cells overexpress the channel TRPC6 as compared to non-tumoral MCF10A and treatment with OLCT for 24–72 h downregulates TRPC6 expression in MDA-MB-231 cells. These findings indicate that OLCT impairs the ability of breast cancer cells to proliferate and migrate via downregulation of TRPC6 channel expression while having no effect on the biology of non-tumoral breast cells.

Abstract C259: Olive phenolics as c-Met inhibitors: Molecular mechanisms mediating the anticancer effects of oleocanthal in breast cancer cells.

Abstract The Mediterranean countries have lower cancer incidence compared to the rest of European countries and the United States. Olive oil is a key ingredient of the Mediterranean diet. Olive oil secoiridoids have showed antiproliferative and apoptotic activity in HER2 overexpressing cancer cells. In addition, oleocanthal, a minor phenolic secoiridoid in extra-virgin olive oil, displays protective activity against inflammatory and Alzheimer's disease. It has been shown that oleocanthal treatment inhibited the growth, migration, and invasion of human breast and prostate cancer cell lines. Oleocanthal was identified via a computer-assisted study as a c-Met activation inhibitor hit, targeting its ATP binding site, and stabilizing the kinase domain in its inactive conformation. It has been reported that oleocanthal competitively inhibited the phosphorylation of c-Met kinase in vitro in the Z’-LYTE assay, however, the exact antiproliferative, antimigratory, and pro-apoptotic mechanisms of oleocanthal are not well understood. In this study, the effects of oleocanthal on cell proliferation, migration and apoptosis in human breast cancer cells were evaluated. Oleocanthal treatment showed a dose-dependent inhibition of HGF-induced cell proliferation as shown by MTT, and Ki-67 immunostaining assay. Additional studies were conducted to determine the intracellular mechanisms mediating oleocanthal's anticancer activity in breast cancer cells. Flow cytometry analysis showed that oleocanthal treatment increased the percentage of cells in G1 phase as compared to the vehicle-treated control group. Western blot studies revealed that blockade in cell cycle progression is associated with regulating the expression of various important G1/S modulators. Additional Western blot experiments showed that oleocanthal treatment caused a marked, dose-dependent decrease of HGF-induced c-Met receptor phosphorylation. Furthermore, oleocanthal treatment was associated with a relatively large suppression in HGF-induced of Erk1/2, Akt, PTK6 phosphorylation as compared to vehicle-treated control group. Additional studies were conducted to investigate whether the growth inhibitory effects of the oleocanthal treatment is associated with a concomitant activation of apoptotic pathways. Results of MTT assay showed that the oleocanthal treatment induced apoptosis at 25 µM. Activation of apoptosis by oleocanthal in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADPribose) polymerase(PARP). Additional studies showed that oleocanthal treatment inhibited HGF-induced migration of cancer cells, and suppressed HGF-induced epithelial-to-mesenchymal transition (EMT), as indicated by wound healing assay and a characteristic increased expression of epithelial cellular markers (E-cadherin, β-catenin) and a corresponding decrease in mesenchymal cellular markers (vimentin). These results suggest that oleocanthal is a promising hit with potential therapeutic use for the control of c-Met-dependent malignancies. This study was supported by the National Cancer Institute, grant number 1R15CA167475-01. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C259. Citation Format: Mohamed R. Akl, Belnaser A. Busnena, Mohamed M. Mohyeldin, Khalid El Sayed. Olive phenolics as c-Met inhibitors: Molecular mechanisms mediating the anticancer effects of oleocanthal in breast cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C259.