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.