Blueberry phytochemicals inhibit growth and metastatic potential of MDA‐MB‐231 breast cancer cells through modulation of the Phosphatidylinositol 3‐Kinase pathway

This study investigated the chemopreventive activity of blueberries in triple negative breast cancer. Blueberry juice decreased cell proliferation and motility of MDA-MB-231 cells and decreased matrix metalloproteinase -9 activity and urokinase-type plasminogen activator secretion while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion. Phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor kappa-B (NFκB) activation was decreased in MDA-MB-231 cells, where protein kinase C and extracellular regulated kinase activity were not affected. In vivo, daily gavage of blueberry juice in MDA-MB-231 xenograft-bearing mice significantly decreased tumor growth through decreased cell proliferation and increased apoptosis compared to controls. Blueberry ingestion decreased activation of AKT and p65 NFκB signaling proteins in tumor samples. Freeze-dried blueberry powder incorporated into the diet showed that 5 and 10% blueberry powder significantly decreased MDA-MB-231 tumor volume. Microarray analysis of tumors from 5% blueberry-fed mice revealed significant changes in genes important to inflammation, cell signaling and metastasis compared to control-fed mice. Metastasis was decreased in mice fed a 5% blueberry diet. These data illustrate the inhibitory effect of blueberry on the growth and metastatic potential of MDA-MB-231 cells.