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Publication : Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids.

First Author  Kahali B Year  2014
Journal  Carcinogenesis Volume  35
Issue  10 Pages  2183-93
PubMed ID  24876151 Mgi Jnum  J:216016
Mgi Id  MGI:5607490 Doi  10.1093/carcin/bgu117
Citation  Kahali B, et al. (2014) Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids. Carcinogenesis 35(10):2183-93
abstractText  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 both in vitro and in vivo.
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