Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line.
The aim of this investigation was to evaluate the chemopreventative/antiproliferative potential of a grape seed proanthocyanidin extract (GSPE) against colon cancer cells (CaCo2 cells) and to investigate its mechanism of action. GSPE (10-100 microg/ml) significantly inhibited cell viability and increased apoptosis in CaCo2 cells, but did not alter viability in the normal colon cell line (NCM460). The increased apoptosis observed in GSPE-treated CaCo2 cells correlated with an attenuation of PI3-kinase (p110 and p85 subunits) and decreased PKB Ser(473) phosphorylation. GSPE might thus exert its beneficial effects by means of increased apoptosis and suppression of the important PI3-kinase survival-related pathway.
Engelbrecht
A-M
AM
Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa. ame@sun.ac.za
Mattheyse
M
M
Ellis
B
B
Loos
B
B
Thomas
M
M
Smith
R
R
Peters
S
S
Smith
C
C
Myburgh
K
K
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D044945:Proanthocyanidins / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012639:Seeds / Q000737:chemistry*; D027843:Vitis / Q000737:chemistry*
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000975:Antioxidants; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D044945:Proanthocyanidins; D017346:Protein Serine-Threonine Kinases; C013221:proanthocyanidin