title: Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kahali
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Marquez
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Thompson
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Sarah J B
authors.initials: SJ
authors.lastname: Gramling
authors.affiliation: Department of Pathology and.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Aponick
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Office 294, Cancer/Genetics Building, 2033 Mowry Road, Gainesville, FL 32611, USA and Department of Pathology and Department of Chemistry, University of Florida, Gainesville, FL 32611, USA dnreisman@ufl.edu.
authors.forename: David
authors.initials: D
authors.lastname: Reisman
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D058990:Molecular Targeted Therapy; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; C084011:SMARCA2 protein, human; D054852:Small Molecule Libraries; C499503:Smarca2 protein, mouse; D014157:Transcription Factors