Inhibition of benzo(a)pyrene diol-epoxide-induced transactivation of activated protein 1 and nuclear factor κB by black raspberry extracts

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

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)6857-6863
Number of pages7
JournalCancer Research
Volume62
Issue number23
StatePublished - Dec 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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