Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells.

Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells.
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通过 EGCG、白藜芦醇和 γ-生育三烯酚的组合协同作用抑制雌激素受体阳性 MCF-7 乳腺癌细胞的细胞增殖和基因表达。

DOI:
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发表时间:
2008
影响因子:
5.2
通讯作者:
Joseph M. Wu
Joseph M. Wu
中科院分区:
医学2区
文献类型:
--
作者:
T. Hsieh;Joseph M. Wu

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许多膳食植物化学物质在体外测试时显示出抗乳腺癌的活性;然而,在大多数情况下,个别植物化学物质的有效性需要在体内不易达到的剂量。因此,饮食是否可能在临床环境和乳腺癌预防中发挥转化承诺和益处仍不清楚。由于癌细胞被赋予复杂的,冗余的,收敛和发散的途径,跨越遗传和代谢网络,而不仅仅是在正常细胞中的复制,它是感兴趣的测试是否涉及较低的,生理相关剂量的天然膳食剂的多组分方法可以开发为乳腺癌的化学预防策略。在此,我们调查,使用雌激素受体阳性的MCF-7乳腺癌细胞作为模型,无论是组合表没食子儿茶素没食子酸酯(EGCG),白藜芦醇和γ-生育三烯酚在次优剂量eliminate协同作用,抑制细胞增殖,调节基因表达,并增加抗氧化活性,与单独添加的三种植物化学物质相比。结果显示,作为单一试剂添加的>或=50 μ M的EGCG、>或=25 μ M的白藜芦醇和>或=10 μ M的γ-生育三烯酚分别对细胞增殖有约33%、50%和58%的抑制。当使用每种植物化学物质的次优剂量(10 μ M)时,观察到白藜芦醇和γ-生育三烯酚的组合对细胞增殖的抑制具有显著的累加效应,而三种植物化学物质加在一起并没有产生更明显的细胞增殖抑制。当γ-生育三烯酚与表没食子儿茶素没食子酸酯或白藜芦醇一起添加时,发现在减少细胞周期蛋白D1和bcl-2表达方面具有显著的累加效应。三种植物化学物质之间的功能协同作用仅在醌还原酶NQO 1的诱导中观察到。这些结果表明,以饮食为基础的保护乳腺癌可能部分来自协同作用之间的膳食植物化学物质针对特定的分子靶点在响应乳腺癌细胞,并提供支持的可行性发展的饮食为基础的组合方法在预防和治疗乳腺癌。
Numerous dietary phytochemicals have shown anti-breast carcinogenic activities when tested in vitro; however, in most cases, the demonstrated efficacy of individual phytochemicals requires doses not readily achievable in vivo. Therefore, whether diets might exert translational promises and benefits in clinical settings and prevention of breast cancer remain unclear. Since cancer cells are endowed with complex, redundant, converging and diverging pathways spanning both the genetic and metabolic networks that are not merely replicates of those in normal cells, it is of interest to test whether a multicomponent approach involving lower, physiologically relevant doses of natural dietary agents may be developed as a chemopreventive strategy for breast cancer. Herein, we investigated, using the estrogen receptor-positive MCF-7 breast cancer cells as a model, whether the combination of epigallocatechin gallate (EGCG), resveratrol and gamma-tocotrienol at suboptimal doses elicits synergism in suppressing cell proliferation, modulating gene expression, and increasing antioxidant activity, as compared to each of the three phytochemicals added alone. The results showed that there was a approximately 33, 50 and 58% inhibition of cell proliferation by > or =50 microM EGCG, > or =25 microM resveratrol and > or =10 microM gamma-tocotrienol, respectively, added as a single agent. When a suboptimal dose (10 microM) of each phytochemical was used, a significant additive effect in suppression of cell proliferation was observed with the combination of resveratrol and gamma-tocotrienol whereas the three phytochemicals added together did not produce more pronounced inhibition of cell proliferation. A significant additive effect in reducing cyclin D1 and bcl-2 expression was found when gamma-tocotrienol was added with either EGCG or resveratrol. Functional synergism among the three phytochemicals was only observed in the induction of quinone reductase NQO1. These results suggest that diet-based protection against breast cancer may partly derive from synergy amongst dietary phytochemicals directed against specific molecular targets in responsive breast cancer cells, and provide support for the feasibility of the development of a diet-based combinatorial approach in the prevention and treatment of breast cancer.
DOI: --
发表时间: 1998-04
期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子: --
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Chung S. Yang;Laishun Chen;Mao-jung Lee;D. Balentine;May-Chen Kuo;S. Schantz
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发表时间: 2000
期刊: The Journal of biological chemistry
影响因子: --
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DOI: 10.1093/jn/132.11.3504s
发表时间: 2002
期刊: The Journal of nutrition.
影响因子: --
作者:
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影响因子: 8.2
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DOI: 10.1016/s0027-5107(02)00330-5
发表时间: 2003-02-01
影响因子: 2.3
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