Endocrine Abstracts

Prostate cancer (PCa) is the second most diagnosed cancer type and the sixth cause of cancer death among men worldwide. Due to the usual slow course of the progression of this disease, there is a growing interest in finding chemopreventive therapeutics with a low risk of side effects. In line with this, recent studies have shown that hydroxytyrosol (HT), one of the main extra virgin olive oil phenolic compounds, exerts a protective role against different cancer types. Moreover, semisynthetic derivatives of HT could improve its bioavailability and pharmacological activities. Thus, in this study we aimed to compare the in vitro anticancer effects of HT and five semisynthetic derivatives, including alkyl ethers, esters, and nitro-derivatives against different PCa cell lines. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac) and ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells, whereas the nitro-derivatives were more cytotoxic in RWPE-1. In addition, HT, HT-Ac and HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 as well as prostatosphere size and colony formation in 22Rv1 cells. Nevertheless, HT-Ac and HT-Et, but not HT, were able to decrease phospho-AKT/AKT levels and colony and prostatosphere formation in PC-3. In sum, our results together with previous studies showing the antioxidant capacity of HT and its lipophilic derivatives suggest that they could be considered as potential therapeutic tools in PCa.

Funding

Junta de Andalucía (PI-0152-2019/RH-0084-2020/BIO-0139), MINECO (PID2019-105564RB-I00/FPU17-00263, FPU16-06190/FPU18-02485), ISCIII (PI16-00264), University of Cordoba (Programa Operativo FEDER Andalucía: 27 416), and CIBERobn.