Inhibition of benzo(a)pyrene diol-epoxide-induced transactivation of activated protein 1 and nuclear factor kappaB by black raspberry extracts. Cancer Res 2002 Dec 01;62(23):6857-63
Date
12/04/2002Pubmed ID
12460899Scopus ID
2-s2.0-0036894353 (requires institutional sign-in at Scopus site) 115 CitationsAbstract
Freeze-dried black raspberries have been shown to inhibit the development of chemically induced esophageal and colon cancer in rodents. In addition, organic extracts of black raspberries inhibit benzo(a)pyrene (BaP)-induced cell transformation in vitro. The molecular mechanisms through which black raspberries inhibit carcinogenesis remain unclear. We investigated the effects of black raspberry extracts on transactivation of activated protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) induced by BaP diol-epoxide (BPDE), the ultimate carcinogen of BaP, in mouse epidermal JB6 Cl 41 (Cl 41) cells. Black raspberries were extracted with methanol, and the methanol extract was partitioned and chromatographed into several fractions designated RU-F003, RU-F004, RU-DM, and RU-ME. Pretreatment of Cl 41 cells with RU-F003, RU-DM, or RU-ME resulted in an inhibition of BPDE-induced AP-1 and NFkappaB activities. The RU-ME fraction was the most potent inhibitor among the fractions tested. In contrast, fraction RU-F004 did not inhibit BPDE-induced AP-1 or NFkappaB activities in Cl 41 cells. The inhibitory effects of RU-ME on BPDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of mitogen activated protein kinase activation and inhibitory subunit kappaB phosphorylation, respectively. Pretreatment of cells with berry fractions did not result in an inhibition of BPDE binding to DNA; thus, this was not a mechanism of reduced AP-1 and NFkappaB activities. None of the fractions was found to affect p53-dependent transcription activity. In view of the important roles of AP-1 and NFkappaB in tumor promotion/progression, these results suggest that the ability of black raspberries to inhibit tumor development may be mediated by impairing signal transduction pathways leading to activation of AP-1 and NFkappaB. The RU-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
Author List
Huang C, Huang Y, Li J, Hu W, Aziz R, Tang MS, Sun N, Cassady J, Stoner GDMESH terms used to index this publication - Major topics in bold
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAnimals
Carcinogens
Cell Line
DNA Adducts
Drug Interactions
Enzyme Activation
Epidermis
Fruit
I-kappa B Proteins
Methanol
Mice
Mitogen-Activated Protein Kinases
NF-KappaB Inhibitor alpha
NF-kappa B
Phosphorylation
Plant Extracts
Rosaceae
Transcription Factor AP-1
Transcriptional Activation
