期刊
ANTIOXIDANTS
卷 10, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/antiox10091348
关键词
anticancer; extra virgin olive oil; hydroxytyrosol; prostate cancer; semisynthetic derivatives
资金
- Junta de Andalucia [PI-0152-2019, BIO-0139, RH-0084-2020, PID2019-105564RB-I00, PID2019-105201RB-I00, FPU17/00263, FPU16/06190, FPU18/02485, 27416]
- Instituto de Salud Carlos III - European Union (ERDF/ESF, Investing in your future) [PI20/01301, CD16/00092]
- CIBERobn
- Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain
The study suggests that hydroxytyrosol (HT) and its lipophilic derivatives could be potential therapeutic tools for prostate cancer (PCa) by demonstrating their anti-proliferative and migration inhibitory effects on PCa cell lines.
A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Because of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据