Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation.
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.
Sirianni
Rosa
R
Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende (CS), Italy.
Chimento
Adele
A
De Luca
Arianna
A
Casaburi
Ivan
I
Rizza
Pietro
P
Onofrio
Arianna
A
Iacopetta
Domenico
D
Puoci
Francesco
F
Andò
Sebastiano
S
Maggiolini
Marcello
M
Pezzi
Vincenzo
V
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D015533:Transcriptional Activation
D016588:Anticarcinogenic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D057888:Iridoid Glucosides; D039823:Iridoids; D047428:Protein Kinase Inhibitors; D011714:Pyrans; C005975:3,4-dihydroxyphenylethanol; C002769:oleuropein; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010626:Phenylethyl Alcohol