Ellagitannin-rich cloudberry inhibits hepatocyte growth factorinduced cell migration and phosphatidylinositol 3-kinase/AKT activation in colon carcinoma cells and tumors in Min mice
Pajari, A.-M., Päivärinta, E., Paavolainen, L., Vaara, E., Koivumäki, T., Garg, R., Heiman-Lindh, A., Mutanen, M., Marjomäki, V., & Ridley, A. J. (2016). Ellagitannin-rich cloudberry inhibits hepatocyte growth factorinduced cell migration and phosphatidylinositol 3-kinase/AKT activation in colon carcinoma cells and tumors in Min mice. Oncotarget, 7(28), 43907-43923. https://doi.org/10.18632/oncotarget.9724
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2016Copyright
© the Authors, 2016. This is an open access article distributed under the terms of a Creative Commons License.
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 freezedried
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.
...
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