Berries have been found to inhibit colon
carcinogenesis in animal models, and thus represent a potential source of compounds for prevention and treatment of
colorectal cancer. The mechanistic basis for their effects is not well understood. We used human colon
carcinoma cells and Min mice to investigate the effects of
ellagitannin-rich cloudberry (Rubus chamaemorus) extract on
cancer cell migration and underlying cell signaling. Intrinsic and
hepatocyte growth factor (HGF) -induced cell motility in human HT29 and HCA7 colon
carcinoma cells was assessed carrying out cell scattering and scratch wound healing assays using time-lapse microscopy. Activation of Met, AKT, and ERK in cell lines and
tumors of cloudberry-fed Min mice were determined using immunoprecipitation, Western blot and immunohistochemical analyses. Cloudberry extract significantly inhibited particularly HGF-induced
cancer cell migration in both cell lines. Cloudberry extract inhibited the Met
receptor tyrosine phosphorylation by HGF and strongly suppressed HGF-induced AKT and ERK activation in both HT29 and HCA7 cells. Consistently, cloudberry feeding (10% w/w freeze-dried berries in diet for 10 weeks) reduced the level of active AKT and prevented phosphoMet localization at the edges in
tumors of Min mice. These results indicate that cloudberry reduces
tumor growth and
cancer cell motility by inhibiting Met signaling and consequent activation of
phosphatidylinositol 3-kinase/AKT in vitro and in
tumors in vivo. As the Met receptor is recognized to be a major target in
cancer treatment, our results suggest that
dietary phytochemicals may have therapeutic value in reducing
cancer progression and
metastasis.