Overview of mechanisms of action of lycopene
Overview of mechanisms of action of lycopene
复制标题
DOI：
10.1177/153537020222701013
复制
发表时间：
2002-11-01
影响因子：
3.2
通讯作者：
Lu, QY
中科院分区：
文献类型：
--
作者：
Heber, D;Lu, QY
许多研究表明，饮食中摄入含有番茄红素的西红柿和番茄产品与降低患癌症和心血管疾病等慢性病的风险有关。血清和组织番茄红素水平也与肺癌和前列腺癌的风险呈负相关。番茄红素是一种非常有效的抗氧化剂，这显然是番茄红素作用的一个主要重要机制。在这方面，番茄红素可以捕获单线态氧，并在Ames测试中减少突变。然而，其他机制的证据也在不断积累。生理浓度的番茄红素可以通过干扰生长因子受体信号转导和细胞周期进程来抑制人类癌细胞的生长，特别是在前列腺癌细胞中，而没有证据表明细胞有毒性作用或细胞凋亡。使用人类和动物细胞的研究已经确定了一个基因，连接蛋白43，它的表达被番茄红素上调，并允许细胞间直接缝隙连接通讯(GJC)。GJC在许多人类肿瘤中是缺乏的，它的恢复或上调与增殖减少有关。低浓度番茄红素与1，25-二羟基维生素D3联合作用对HL-60早幼粒白血病细胞株的增殖和分化有协同作用，对细胞周期进程有相加作用，提示在核或亚细胞水平上存在一定的相互作用。番茄红素和叶黄素的结合作为抗氧化剂协同作用，这可能与不同的类胡萝卜素在细胞膜中的特定位置有关。这篇综述将集中于越来越多的证据表明，类胡萝卜素在实验系统中具有意想不到的生物效应，其中一些可能有助于在致癌模型中预防癌症。考虑到体外的溶解性，与人体通过饮食方式获得的剂量的比较，与其他植物化学物质的相互作用，以及其他潜在的机制，如刺激异生代谢、抑制胆固醇生成、调节环氧合酶途径和抑制炎症。这篇综述将指出未来研究的领域，需要更多关于番茄红素对慢性病病因学影响的证据。
Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in numerous studies. Serum and tissue lycopene levels have also been inversely related to the risk of lung and prostate cancers. Lycopene functions as a very potent antioxidant, and this is clearly a major important mechanism of lycopene action. In this regard, lycopene can trap singlet oxygen and reduce mutagenesis in the Ames test. However, evidence is accumulating for other mechanisms as well. Lycopene at physiological concentrations can inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression specifically in prostate cancer cells without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin 43, whose expression is upregulated by lycopene and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. The combination of low concentrations of lycopene with 1,25-dihydroxy-vitamin D3 exhibits a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression in the HL-60 promyelocytic leukemia cell line, suggesting some interaction at a nuclear or subcellular level. The combination of lycopene and lutein synergistically interact as antioxidants, and this may relate to specific positioning of different carotenoids in membranes. This review will focus on the growing body of evidence that carotenoids have unexpected biologic effects in experimental systems, some of which may contribute to their cancer preventive properties in models of carcinogenesis. Consideration of solubility in vitro, comparison with doses achieved in humans by dietary means, interactions with other phytochemicals, and other potential mechanisms such as stimulation of xenobiotic metabolism, inhibition of cholesterogenesis, modulation of cyclooxygenase pathways, and inhibition of inflammation will be considered. This review will point out areas for future research where more evidence is needed on the effects of lycopene on the etiology of chronic disease.