Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids.
Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids.
复制标题
六个结构组中每一个的类黄酮都会重新激活 BRM，而 BRM 可能是类黄酮抗癌作用的辅助因子。
DOI：
10.1093/carcin/bgu117
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发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Reisman,David
中科院分区：
文献类型：
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作者：
Kahali,Bhaskar;Marquez,StefanieB;Thompson,KennethW;Yu,Jinlong;Gramling,SarahJB;Lu,Li;Aponick,Aaron;Reisman,David
黄酮类化合物已被广泛研究，并被充分证明具有抗癌作用，但尚不完全清楚它们如何影响细胞机制以引起这些作用。在这项研究的过程中，我们发现，各种不同的类黄酮很容易恢复BRM缺陷癌细胞系中的Brahma（BRM）。来自六个不同结构组中的每一个的黄酮类化合物在诱导BRM表达以及抑制这些BRM缺陷癌细胞中的生长方面是有效的。通过用shRNA阻断BRM的诱导，我们发现黄酮类化合物诱导的生长抑制是BRM依赖的。我们还发现类黄酮可以通过逆转BRM乙酰化来恢复BRM功能。此外，我们观察到，一系列天然类黄酮含有产品既诱导BRM表达，以及脱乙酰化的BRM蛋白。我们还测试了两种BRM诱导类黄酮（Rynthaline和Diosmin）在低剂量和高剂量下对已建立的小鼠肺癌模型中肿瘤发展的影响。我们发现，这些黄酮类化合物有效地阻止了野生型小鼠肺腺瘤的发展，但在BRMnull小鼠中却没有。这些数据表明，BRM的表达和功能受到类黄酮的调节，并且功能性BRM似乎是类黄酮体外和体内抗癌作用的先决条件。
Flavonoids have been extensively studied and are well documented to have anticancer effects, but it is not entirely known how they impact cellular mechanisms to elicit these effects. In the course of this study, we found that a variety of different flavonoids readily restored Brahma (BRM) in BRM-deficient cancer cell lines. Flavonoids from each of the six different structural groups were effective at inducing BRM expression as well as inhibiting growth in these BRM-deficient cancer cells. By blocking the induction of BRM with shRNA, we found that flavonoid-induced growth inhibition was BRM dependent. We also found that flavonoids can restore BRM functionality by reversing BRM acetylation. In addition, we observed that an array of natural flavonoid-containing products both induced BRM expression as well as deacetylated the BRM protein. We also tested two of the BRM-inducing flavonoids (Rutin and Diosmin) at both a low and a high dose on the development of tumors in an established murine lung cancer model. We found that these flavonoids effectively blocked development of adenomas in the lungs of wild-type mice but not in that of BRMnull mice. These data demonstrate that BRM expression and function are regulated by flavonoids and that functional BRM appears to be a prerequisite for the anticancer effects of flavonoids bothin vitroandin vivo.