A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.
A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.
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白藜芦醇类似物的甲氧基衍生物在转化的成纤维细胞中选择性诱导线粒体凋亡途径的激活。
DOI：
10.1038/sj.bjc.6602300
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发表时间：
2005-02-14
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
白藜芦醇 (R-3) 是一种来自葡萄的三羟基反式二苯乙烯，可抑制动物模型中的多阶段致癌作用。白藜芦醇衍生物 3,4,5,4'-四羟基芪 (R-4) 对转化的人类细胞表现出有效的生长抑制作用。在此，我们报道，由 R-4 转化而来的 3,4,5,4'-四甲氧基二苯乙烯 (MR-4) 在测试浓度下对癌细胞系（WI38VA、IMR-90SV、HeLa、LNCaP、HT-29 和 HepG2）更有效，但对正常细胞（WI38、IMR-90、BJ-T）的生长几乎没有抑制作用。 MR-4对转化的WI38VA人细胞生长抑制的IC50值为0.5μM，而正常WI38细胞的IC50值大于50μM。然而，白藜芦醇没有表现出如此明显的差异效应，R-3对WI38VA细胞的IC50值约为50μM。 MR-4的生长抑制作用与转化细胞中细胞凋亡的诱导相关。当比较正常 WI38 细胞和转化的 WI38VA 细胞时，MR-4 诱导转化细胞中 Bax/Bcl-2 mRNA 比率、p53 和 Bax 蛋白水平、半胱天冬酶激活和 DNA 片段增加，但在正常细胞中则不然。进一步分析显示，MR-4 在 WI38VA 中引起线粒体核周聚集的快速出现，但在 WI38 细胞中则不然，这表明线粒体可以作为 MR-4 的早期靶点。 R-3 也能诱导细胞凋亡和线粒体聚集，但浓度要高得多，接近 500 μM。综上所述，线粒体介导的细胞凋亡途径的特异性激活可能是 MR-4 具有显着差异生长抑制作用的主要原因。
Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4′-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4′-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 μM, as compared to the value of greater than 50 μM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 μM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 μM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.
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影响因子：
9.7
作者：
Bernhard, D;Schwaiger, W;Csordas, A
通讯作者：
Csordas, A
影响因子：
2.9
作者：
Ding, Xian-Zhong;Adrian, Thomas E
通讯作者：
Adrian, Thomas E
影响因子：
4.7
作者：
Lu, JB;Ho, CT;Chen, KY
通讯作者：
Chen, KY
DOI：
10.1073/pnas.77.2.990
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
JOHNSON, LV;WALSH, ML;CHEN, LB
通讯作者：
CHEN, LB
DOI：
10.1111/j.1749-6632.2002.tb02918.x
发表时间：
2002-01-01
期刊：
ALCOHOL AND WINE IN HEALTH AND DISEASE
影响因子：
--
作者：
Bhat, KPL;Pezzuto, JM
通讯作者：
Pezzuto, JM