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Lowbush Blueberry Component Pterostilbene Inhibits the Matrix Metalloproteinase and the Urokinase Signaling Systems in Human Prostate Cancer Cells Via Alterations in Cellular Signal Transduction Pathways
Author(s) -
Stetson Colin,
Kim Joseph,
Elwood Benjamin,
McCallum Jason,
Hurta Robert
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.894.1
Subject(s) - pterostilbene , signal transduction , prostate cancer , matrix metalloproteinase , microbiology and biotechnology , cancer research , chemistry , cancer , medicine , biology , biochemistry , resveratrol
Wild blueberry extracts were shown to inhibit MMP‐2 & MMP‐9 activity in DU145 human prostate cancer cells in vitro. This study examined the effects of pterostilbene (PT) on MMP & uPA activities in DU145 cells. PT (30uM)(6h) inhibited MMP‐2/‐9 activity. PT decreased cellular viability ~10% post 6 h. exposure. PT treatment increased TIMP‐1/‐2 & decreased EMMPRIN & RECK expression. PT treatment decreased uPA & uPAR and increased PAI‐1/‐2 protein expression. PT treatment resulted in increased expression of pERK‐1, pERK‐2 & ERK‐1. PT decreased p‐p38 & p38 protein levels. No apparent change in either ERK‐2, JNK‐1 & JNK‐2 or p‐JNK‐2 expression was noted. PT did increase p‐JNK‐1 protein levels. PT increased expression of p‐Akt & P‐I‐3 kinase p85 with no apparent change in either Akt or P‐I‐3 kinase p110 protein expression levels. PT also increased JAK1, STAT3 & STAT4 expression & decreased JAK2 & STAT1 expression with no apparent change in either JAK3 or STAT2 expression. PT decreased cytosolic p65 and nuclear p50 & increased cytosolic p50 & increased IkB & c‐fos and c‐jun expression. PT can inhibit MMP‐2/‐9 & uPA activities by affecting cellular signalling. (Telus Motorcycle Ride for Dad (PEI Division) Prostate Cancer Research Fund)