Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours.
METHODS
Hydroxytyrosol (a phenolic compound derived from virgin olive oil) has demonstrated an anti-tumour effect in several tumour cell lines in addition to other health-related properties. The aim of this study was to investigate, for the first time in an animal model of experimental mammary carcinoma, the anti-cancer ability of hydroxytyrosol and to discover which pathways are modified by hydroxytyrosol.


RESULTS
Dimethylbenz[α]anthracene-induced mammary tumours were induced in 28 female Sprague-Dawley rats and ten of them were treated with hydroxytyrosol (0.5 mg/kg b.w. 5 days/week for 6 wk). cDNA microarray and quantitative RT-PCR experiments were performed. Hydroxytyrosol was found to inhibit the experimental mammary tumour growth and proliferation rate, with results comparable to those of doxorubicin but better with regard to the histopathological outcome. It also altered the expression of genes related to apoptosis, cell cycle, proliferation, differentiation, survival and transformation pathways.


CONCLUSIONS
This study shows that hydroxytyrosol exerts anti-cancer effects in Sprague-Dawley rats with experimental mammary tumours, inhibiting growth and cell proliferation in mammary tumours. Moreover, hydroxytyrosol alters several genes associated with cell proliferation, apoptosis and the Wnt signalling pathway, promoting a high expression of Sfrp4. However, further studies are necessary to better understand the mechanisms of hydroxytyrosol.
Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain.
Sergio
S
Granados-Principal
Jose L
JL
Quiles
Cesar
C
Ramirez-Tortosa
Pedro
P
Camacho-Corencia
Pedro
P
Sanchez-Rovira
Laura
L
Vera-Ramirez
M Carmen
MC
Ramirez-Tortosa
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D046228:Microarray Analysis; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008517:Phytotherapy; D010938:Plant Oils / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094742:Secreted Frizzled-Related Proteins
D000972:Antineoplastic Agents, Phytogenic; D000069463:Olive Oil; D010626:Phenylethyl Alcohol; D010938:Plant Oils; D011518:Proto-Oncogene Proteins; C498455:Sfrp4 protein, rat; D000094742:Secreted Frizzled-Related Proteins; C005975:3,4-dihydroxyphenylethanol