Affiliations: Institute of Biochemistry and Molecular Medicine,
University of Bern, Bern, Switzerland
Note: [] Address for correspondence: J.M. Zingg, Institute of
Biochemistry and Molecular Medicine, Bühlstrasse 28, 3012 Bern,
Switzerland. Tel.: +41 31 631 41 18; Fax: +41 31 631 37 37; E-mail:
zin34@swissonline.ch
Abstract: The tocopherols (α, β-, γ-, and
δ-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 μM δ-tocopherol and 50 μM
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 δ-tocopherol and resveratrol combinatory treatment. Resveratrol acts
more efficiently as an inhibitor of PKB phosphorylation than α-, β-, γ-tocopherols,
whereas δ-tocopherol shows a stronger inhibition
possibly as a result of its apoptotic secondary effects. Our data suggest that
δ-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.
