Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells

Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells
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DOI:
10.1016/j.fct.2010.10.014
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发表时间:
2011-01-01
影响因子:
4.3
通讯作者:
Sayadi, Sami
Sayadi, Sami
中科院分区:
农林科学2区
文献类型:
--
作者:
Bouallagui, Zouhaier;Han, Junkuy;Sayadi, Sami

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橄榄(Olea europea L.)叶子已被大量开发用于预防或治疗高血压、致癌、糖尿病、动脉粥样硬化和许多其它传统治疗用途。这些活动被认为是橄榄微量营养素,特别是多酚的输出。羟基酪醇和橄榄苦苷被认为是橄榄叶中的主要多酚化合物。在这项工作中,研究了富含羟基酪醇的橄榄叶提取物的潜在抗肿瘤活性。采用MTT和中性红试验检测了对MCF-7乳腺癌细胞的体外细胞毒性作用。采用流式细胞术和免疫印迹法进一步研究其抗肿瘤活性。细胞毒性试验导致MCF-7细胞的剂量依赖性生长抑制。这种抑制是由于细胞周期停滞在G 0/G1期。对橄榄叶提取物抑制细胞生长的分子机制的理解表明肽基脯氨酰顺反异构酶Pin 1的表达下调,这反过来又降低了G1关键蛋白的水平;细胞周期蛋白D1。此外,橄榄叶提取物处理上调了AP 1转录因子成员c-jun。因此,橄榄叶提取物作为预防癌症的食品添加剂的可能用途需要进一步深入研究。(c)2010爱思唯尔有限公司版权所有。
Throughout the history, olive (Olea europea L.) leaves have been heavily exploited for the prevention or the treatment of hypertension, carcinogenesis, diabetes, atherosclerosis and so many other traditional therapeutic uses. These activities are thought to be the output of olive micronutrients especially polyphenols. Hydroxytyrosol and oleuropein are considered as major polyphenolic compounds in olive leaf. In this work, a hydroxytyrosol rich olive leaves extract was investigated for potential anti-tumoral activities. In vitro cytotoxic effects against MCF-7 breast cancer cells were examined using MTT and neutral red tests. The anti-tumor activities were further investigated by flow cytometry and western blotting. Cytotoxicity assays resulted in a dose dependent growth inhibition of MCF-7 cells. This inhibition was due to the cell cycle arrest in the G0/G1 phase. The understanding of the molecular mechanism by which olive leaves extract arrested cell growth showed a down-expression of the peptidyl-prolyl cis-trans isomerase Pin1 which in turn decreased the level of a G1 key protein; Cyclin D1. Additionally, olive leaves extract treatment up-regulated the AP1 transcription factor member, c-jun. Therefore, olive leaves extract will necessitate further deep investigation for a probable use as a cancer preventive food additive. (c) 2010 Elsevier Ltd. All rights reserved.