Sage components enhance cell death through nuclear factor kappa-B signaling

Front Biosci (Elite Ed). 2011 Jan 1;3:410-20. doi: 10.2741/e256.

Abstract

The sage components linalyl acetate (Ly) and alpha-terpineol (Te) exhibit synergistic anti-proliferative effects. We investigated the effects of Ly and Te on NF-kappaB signaling in HCT-116 colon cancer cells. Ly and Te combinations dose-dependently reduced HCT-116 viability at non-cytotoxic concentrations. Combination treatment induced 30%-60% increase in PreG1 through induction of apoptosis and necrosis. DNA binding assays revealed that combination treatment suppressed both basal and TNF-alpha-induced NF-kappaB activation. This suppression correlated with the inhibition of p65 nuclear translocation and IkappaB-alpha degradation. The lack of change in IKK expression levels or inhibition in IkappaB-alpha phosphorylation suggest the involvement of an IKK-independent mechanism. Ly and Te combination was found to downregulate the expression of NF-kappaB-regulated antiapoptotic and proliferative gene products. Separate treatments and drug combinations significantly decreased DNA binding activity of NF-kappaB which led to the potentiation of cell death induced by the colon cancer drugs oxaliplatin and 5-FU. These results indicate that Ly and Te anticancer activities are partly mediated through the suppression of NF-kappaB activation, suggesting their use in combination with chemotherapeutic agents to induce apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cyclohexane Monoterpenes
  • Cyclohexenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Flow Cytometry
  • HCT116 Cells
  • Humans
  • Immunohistochemistry
  • Monoterpenes / pharmacology*
  • NF-kappa B / metabolism*
  • Oligonucleotides / genetics
  • Plant Extracts / pharmacology*
  • Salvia officinalis / chemistry*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Annexin A5
  • Cyclohexane Monoterpenes
  • Cyclohexenes
  • Monoterpenes
  • NF-kappa B
  • Oligonucleotides
  • Plant Extracts
  • alpha-terpineol
  • linalyl acetate