Enhanced anti-proliferative effects of combinatorial treatment of delta-tocopherol and resveratrol in human HMC-1 cells.
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.
Reiter
Elke
E
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Azzi
Angelo
A
Zingg
Jean-Marc
JM
D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008407:Mast Cells / Q000187:drug effects; D034801:Mastocytoma; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D024505:Tocopherols / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology; D024503:beta-Tocopherol / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013267:Stilbenes; D024504:gamma-Tocopherol; D024503:beta-Tocopherol; D051057:Proto-Oncogene Proteins c-akt; D024502:alpha-Tocopherol; C479072:delta-tocopherol; D000077185:Resveratrol; D024505:Tocopherols