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-KB signaling in HCT-116 colon cancer cells. Ly and Te combinations dose-dependently reduced HCT-116 viability at non-cytotoxic concentrations. Combination treatment induced 30percent-60percent increase in PreG 1 through induction of apoptosis and necrosis. DNA binding assays revealed that combination treatment suppressed both basal and TNFalpha- induced NF-KB activation. This suppression correlated with the inhibition of p65 nuclear translocation and IKB-alpha degradation. The lack of change in IKK expression levels or inhibition in IKB-alpha phosphorylation suggest the involvement of an IKKindependent mechanism. Ly and Te combination was found to downregulate the expression of NF- KB-regulated antiapoptotic and proliferative gene products. Separate treatments and drug combinations significantly decreased DNA binding activity of NF-KB 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- KB activation, suggesting their use in combination with chemotherapeutic agents to induce apoptosis.