Fabiani Roberto, De Bartolomeo Angelo, Rosignoli Patrizia, Servili Maurizio, Selvaggini Roberto, Montedoro Gian Francesco, Di Saverio Cristina, Morozzi Guido
Dipartimento di Specialità Medico-Chirurgiche e Sanità Pubblica, Sezione di Epidemiologia Molecolare ed Igiene Ambientale, Università degli Studi di Perugia, Italy.
J Nutr. 2006 Mar;136(3):614-9. doi: 10.1093/jn/136.3.614.
Although epidemiologic evidence and animal studies suggest that olive oil may prevent the onset of cancer, the components responsible for such an effect and their mechanisms of action remain largely unknown. In the present study, we investigated the effect of a virgin olive oil phenol extract (PE) on proliferation, the cell cycle distribution profile, apoptosis, and differentiation of the human promyelocytic cell line HL60. PE inhibited HL60 cell proliferation in a time- and concentration-dependent manner, as demonstrated by the viable cell count and 3-[4,5-dimethyl(thiazol-2-yl)]-3,5-diphenyltetrazolium bromide (MTT) metabolism. Cell growth was completely blocked at a PE concentration of 13.5 mg/L; apoptosis was also induced as detected by fluorescence microscopy and flow cytometry. Determination of the cell cycle distribution by flow cytometry revealed an accumulation of cells in the G(0)/G(1) phase. Two compounds isolated from PE, the dialdehydic forms of elenoic acid linked to hydroxytyrosol (3,4-DHPEA-EDA) and to tyrosol (pHPEA-EDA), were shown to possess properties similar to those of PE; they account for a part of the powerful effects exerted by the complex mixture of compounds present in PE. The concentrations of the different compounds in PE were determined by HPLC, and the purity of 3,4-DHPEA-EDA and pHPEA-EDA was ascertained by NMR. Treatment with PE induced a differentiation in HL60 cells, which subsequently acquired the ability to produce superoxide ions and reduce nitroblue tetrazolium to formazan. These results support the hypothesis that polyphenols play a critical role in the anticancer activity of olive oil.
尽管流行病学证据和动物研究表明橄榄油可能预防癌症的发生，但其发挥这种作用的成分及其作用机制在很大程度上仍不清楚。在本研究中，我们调查了初榨橄榄油酚提取物（PE）对人早幼粒细胞系HL60的增殖、细胞周期分布、凋亡及分化的影响。如活细胞计数和3-[4,5-二甲基（噻唑-2-基）]-3,5-二苯基溴化四氮唑（MTT）代谢所显示，PE以时间和浓度依赖性方式抑制HL60细胞增殖。在PE浓度为13.5mg/L时细胞生长完全被阻断；通过荧光显微镜和流式细胞术检测也诱导了凋亡。流式细胞术测定细胞周期分布显示细胞在G(0)/G(1)期积累。从PE中分离出的两种化合物，即与羟基酪醇（3,4-DHPEA-EDA）和酪醇（pHPEA-EDA）相连的elenoic酸的二醛形式，显示出与PE相似的性质；它们解释了PE中存在的化合物复杂混合物所发挥的部分强大作用。通过高效液相色谱法测定PE中不同化合物的浓度，并通过核磁共振确定3,4-DHPEA-EDA和pHPEA-EDA的纯度。用PE处理诱导HL60细胞分化，随后其获得产生超氧离子并将硝基蓝四氮唑还原为甲臜的能力。这些结果支持多酚在橄榄油抗癌活性中起关键作用这一假说。
