title: Sage components enhance cell death through nuclear factor kappa-B signaling.
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.
authors.affiliation: Department of Biology, American University of Beirut, Beirut, Lebanon.
authors.forename: Sally Joseph
authors.initials: SJ
authors.lastname: Deeb
authors.forename: Chirine Omar
authors.initials: CO
authors.lastname: El-Baba
authors.forename: Saadia Bashir
authors.initials: SB
authors.lastname: Hassan
authors.forename: Rolf Lennart
authors.initials: RL
authors.lastname: Larsson
authors.forename: Hala Uthman
authors.initials: HU
authors.lastname: Gali-Muhtasib
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D027543:Salvia officinalis / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D017304:Annexin A5; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D039821:Monoterpenes; D016328:NF-kappa B; D009841:Oligonucleotides; D010936:Plant Extracts; C016775:alpha-terpineol; C074463:linalyl acetate