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Cytotoxic effect of hydroxytyrosol and its semisynthetic derivatives against prostate cancer cells
* 1, 2, 3, 4 , 1, 2, 3, 4 , 1, 2, 3, 4 , 1, 2, 3, 4 , 1, 2, 3, 4 , 1, 3, 5 , 6 , 1, 2, 3, 4 , 6 , 1, 2, 3, 4 , * 1, 2, 3, 4
1  Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain
2  Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
3  Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
4  CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
5  Urology Service, HURS/IMIBIC, 14004 Cordoba, Spain
6  Department of Organic and Pharmaceutical Chemistry, University of Seville, 41012 Seville, Spain

Abstract:

Intake of olive oil as the main source of fat in Mediterranean diet is related to positive effects on human health. The olive biophenol hydroxytyrosol (HT) is considered a promising cancer chemopreventive compound against different types of cancer. The aim of the present study was to compare the cytotoxic activity against prostate cancer (PCa) cell lines of HT, obtained from olive mill wastewaters, and five semisynthetic alkyl ether, ester, and nitro-derivatives. HT, hydroxytyrosyl acetate (HT-Ac) and ethyl hydroxytyrosyl ether (HT-Et) exerted higher cytotoxic effect against 22Rv1 and PC-3 PCa cell lines than in non-malignant RWPE-1 cells. These compounds also significantly decreased the migration rate of RWPE-1 and PC-3 cells and the colony and prostatosphere formation of 22Rv1 cells. However, HT-Ac and HT-Et, but not HT, were able to decrease p-AKT levels and colony and prostatosphere formation in PC-3. In sum, HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

Keywords: Anticancer; extra virgin olive oil; hydroxytyrosol; hydroxytyrosyl acetate; prostate cancer; semisynthetic derivatives
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