Oleuropein and hydroxytyrosol inhibit MCF‐7 breast cancer cell proliferation interfering with ERK1/2 activation

Abstract

The growth of many breast tumors is stimulated by estradiol (E2), which activates a classic mechanism of regulation of gene expression and signal transduction pathways inducing cell proliferation. Polyphenols of natural origin with chemical similarity to estrogen have been shown to interfere with tumor cell proliferation. The aim of this study was to investigate whether hydroxytyrosol (HT) and oleuropein (OL), two polyphenols contained in extra-virgin olive oil, can affect breast cancer cell proliferation interfering with E2-induced molecular mechanisms. Both HT and OL inhibited proliferation of MCF-7 breast cancer cells. Luciferase gene reporter experiments, using a construct containing estrogen responsive elements able to bind estrogen receptor alpha (ERalpha) and the study of the effects of HT or OL on ERalpha expression, demonstrated that HT and OL are not involved in ERalpha-mediated regulation of gene expression. However, further experiments pointed out that both OL and HT determined a clear inhibition of E2-dependent activation of extracellular regulated kinase1/2 belonging to the mitogen activating protein kinase family. Our study demonstrated that HT and OL can have a chemo-preventive role in breast cancer cell proliferation through the inhibition of estrogen-dependent rapid signals involved in uncontrolled tumor cell growth.

Antiproliferative effect of oleuropein in prostate cell lines

“…2). These data are in agreement with those from other studies and confirm the involvement of oxidative stress in the oleuropein toxicity (44,45). In addition, our results suggest that DU145 cells show a different susceptibility to necrosis induced by oleuropein.…”

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 the p53 Pathway in Breast Cancer Cells

“…Some epidemiological studies showed correlation between olive products consumption and incidence of breast cancer. Due to its little mild side effects, oleuropein is required as one of the phenolic compounds in olive with a powerful effect on inhibiting the proliferation and migration of cancer cells (Sirianni et al, 2010;Santiago-Mora et al, 2011). Oleuropein can also target steps in cancer progression (Abe et al, 2011).…”