Enhanced anti-proliferative effects of combinatorial treatment of δ-tocopherol and resveratrol in human HMC-1 cells

Elke Reiter, Angelo Azzi, Jean Marc Zingg

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)67-77
Number of pages11
JournalBioFactors
Volume30
Issue number2
DOIs
StatePublished - 2007
Externally publishedYes

Keywords

  • Akt
  • Mast cells
  • Proliferation
  • Resveratrol
  • Tocopherol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Clinical Biochemistry

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