Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours
Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours
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DOI：
10.1002/mnfr.201000220
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发表时间：
2011-05-01
影响因子：
5.2
通讯作者：
Ramirez-Tortosa, MCarmen
中科院分区：
文献类型：
--
作者：
Granados-Principal, Sergio;Quiles, Jose L.;Ramirez-Tortosa, MCarmen
适用范围：羟基酪醇（一种来自初榨橄榄油的酚类化合物）除了具有其他健康相关的特性外，还在几种肿瘤细胞系中表现出抗肿瘤作用。方法和结果：在28只雌性Sprague-Dawley大鼠中诱导二甲基苯并[a]蒽诱导的乳腺肿瘤，其中10只用羟基酪醇（0.5 mg/kg b.w. 5天/周，共6周）。cDNA微阵列和定量RT-PCR实验。发现羟基酪醇抑制实验性乳腺肿瘤生长和增殖率，结果与阿霉素相当，但在组织病理学结果方面更好。它也改变了相关的基因的表达，细胞凋亡，细胞周期，增殖，分化，生存和转化pathways.Conclusions：这项研究表明，羟基酪醇发挥抗癌作用，在Sprague-Dawley大鼠实验性乳腺肿瘤，抑制生长和细胞增殖的乳腺肿瘤。此外，羟基酪醇改变与细胞增殖、凋亡和Wnt信号通路相关的几个基因，促进Sfrp 4的高表达。然而，进一步的研究是必要的，以更好地了解羟基酪醇的机制。
Scope: 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.Methods and results: Dimethylbenz[a] 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.