Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine AACR Conference on Molecular Diagnostics
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[Cancer Research 62, 6857-6863, December 1, 2002]
© 2002 American Association for Cancer Research

Epidemiology and Prevention

Inhibition of Benzo(a)pyrene Diol-Epoxide-induced Transactivation of Activated Protein 1 and Nuclear Factor {kappa}B by Black Raspberry Extracts1

Chuanshu Huang2, Yi Huang3, Jingxia Li, Wenwei Hu, Robeena Aziz, Moon-shong Tang, Nanjun Sun, John Cassady and Gary D. Stoner

Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987 [C. H., Y. H., J. L., W. H., M-s. T.], and Division of Environmental Health Sciences, School of Public Health [R. A., G. D. S.] and College of Pharmacy [N. S., J. C.], The Ohio State University, Columbus, Ohio 43210

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 {kappa}B (NF{kappa}B) 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 NF{kappa}B 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 NF{kappa}B activities in Cl 41 cells. The inhibitory effects of RU-ME on BPDE-induced activation of AP-1 and NF{kappa}B appear to be mediated via inhibition of mitogen activated protein kinase activation and inhibitory subunit {kappa}B 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 NF{kappa}B activities. None of the fractions was found to affect p53-dependent transcription activity. In view of the important roles of AP-1 and NF{kappa}B 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 NF{kappa}B. The RU-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.




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Copyright © 2002 by the American Association for Cancer Research.