Molecular mechanisms involved in chemoprevention of black raspberry extracts: from transcription factors to their target genes.
Berries have attracted attention for their chemopreventive activities in last a few years. Dietary freeze-dried blackberries have been shown to reduce esophagus and colon cancer development induced by chemical carcinogen in rodents. To elucidate molecular mechanisms involved in chemoprevention by berry extracts, we employed mouse epidermal Cl 41 cell line, a well-characterized in vitro model in tumor promotion studies. Pretreatment of Cl 41 cells with methanol-extracted blackberry fraction RO-ME resulted in a dramatical inhibition of B(a)PDE-induced activation of AP-1 and NFkB, and expression of VEGF and COX-2. The inhibitory effects of RO-ME on B(a)PDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of MAPKs and IkappaBalpha phosphorylation, respectively. In view of the important roles of AP-1, NFkappaB, VEGF and COX-2 in tumor promotion/progression, and VEGF and COX-2 are target of AP-1 and NFkappaB, we anticipate 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, subsequently resulting in down-regulation of VEGF and COX-2 expression. The RO-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
Lu
Haitian
H
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Li
Jingxia
J
Zhang
Dongyun
D
Stoner
Gary D
GD
Huang
Chuanshu
C
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics; D004852:Epoxy Compounds / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects*; D000432:Methanol; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D027824:Rosaceae / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D016588:Anticarcinogenic Agents; D001578:Benzopyrans; D004852:Epoxy Compounds; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C482278:benzo(a,l)pyrene diol epoxide; D051546:Cyclooxygenase 2; D000432:Methanol