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白藜芦醇及其衍生物的化学预防作用。

Chemopreventive effects of resveratrol and resveratrol derivatives.

机构信息

Institute for Laboratory Medicine, Department for Medical, Medical University of Vienna, General Hospital of Vienna, Austria.

出版信息

Ann N Y Acad Sci. 2011 Jan;1215:89-95. doi: 10.1111/j.1749-6632.2010.05864.x.

Abstract

Resveratrol is considered to have a number of beneficial effects. Recently, our group modified the molecule and synthesized a number of compounds with different biochemical effects. Polymethoxy and polyhydroxy derivatives of resveratrol were shown to inhibit tumor cell growth in various cell lines and inflammation pathways (cyclooxygenases activity), in part more effectively than resveratrol itself. One lead compound (hexahydroxystilbene, M8) turned out to be the most effective inhibitor of tumor cell growth and of cyclooxygenase 2 activity. M8 was then studied in two different human melanoma mouse models. This novel resveratrol analog was able to inhibit melanoma tumors in a primary tumor model alone and in combination with dacarbacine, an anticancer compound that is used for melanoma treatment. We also tested the development of lymph node metastasis in a second melanoma model and again M8 successfully inhibited the tumor as well as the size and weight of lymph node metastasis. Hydroxylated resveratrol analogs therefore represent a novel class of anticancer compounds and promising candidates for in vivo studies.

摘要

白藜芦醇被认为具有许多有益的作用。最近,我们的研究小组对该分子进行了修饰,并合成了许多具有不同生化作用的化合物。多甲氧基和多羟基白藜芦醇衍生物被证明可以抑制多种细胞系中的肿瘤细胞生长和炎症途径(环氧化酶活性),在某些方面比白藜芦醇本身更有效。一种先导化合物(六羟基二苯乙烯,M8)是最有效的肿瘤细胞生长和环氧化酶 2 活性抑制剂。然后,我们在两种不同的人黑色素瘤小鼠模型中对 M8 进行了研究。这种新型白藜芦醇类似物能够单独抑制原发性肿瘤模型中的黑色素瘤肿瘤,并且与用于黑色素瘤治疗的抗癌化合物达卡巴嗪联合使用。我们还在第二个黑色素瘤模型中测试了淋巴结转移的发展,M8 再次成功地抑制了肿瘤以及淋巴结转移的大小和重量。因此,羟基化白藜芦醇类似物代表了一类新型的抗癌化合物,是体内研究的有前途的候选药物。

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