The
tocopherols (alpha, beta-, gamma-, and
delta-tocopherol) and
resveratrol are
phytochemicals with alleged beneficial effects against
atherosclerosis,
vascular diseases and different
cancers. They both can act as
antioxidants, but they also modulate signal transduction and gene expression by non-
antioxidant mechanisms. Here we wanted to determine whether the combined treatment of mast cells with the two compounds inhibits cell proliferation more efficiently when compared to individual treatments. Both compounds inhibit HMC-1
mastocytoma cell proliferation and reduce the activity of
Protein Kinase B (PKB/Akt) by inhibiting its Ser473-phosphorylation. The combination of 50 microM
delta-tocopherol and 50 microM
resveratrol inhibits proliferation of HMC-1 cells more efficiently when compared to single treatments. In line with this, PKB Ser473-phosphorylation is inhibited best by
delta-tocopherol and
resveratrol combinatory treatment.
Resveratrol acts more efficiently as an inhibitor of PKB phosphorylation than alpha-, beta-, gamma-
tocopherols, whereas
delta-tocopherol shows a stronger inhibition possibly as a result of its apoptotic secondary effects. Our data suggest that
delta-tocopherol and
resveratrol can act additively in reducing cell proliferation and PKB phosphorylation. The combination of
phytochemicals with relatively broad specificity on
enzymes involved in signal transduction and gene expression may increase their activity in disease prevention by modulating several different molecular targets.