Antinflammatory and anticancer effects of terpenes from oily fractions of Teucruim alopecurus, blocker of IκBα kinase, through downregulation of NF-κB activation, potentiation of apoptosis and suppression of NF-κB-regulated gene expression

Teucrium alopecurus is an endemic plant limited to southern Tunisia. In the present study, the chemical composition, anticancer and nuclear factor-kappa B (NF-kappa B) inhibitory effects of Teucrium alopecurus leaf essential oil was investigated. The analysis of Teucrium alopecurus (TA-1) with Gas Chromatography-Mass Spectrometry (GC/MS) showed that alpha-Bisabolol, (+)-epi-Bicyclosesquiphellandrene and alpha-Cadinol, were found in relatively high amounts (16.16%, 15.40% and 8.52%, respectively). Cell viability was determined by 3-(4-5-dimethylthiazol-2-yl) 2-5-diphenyl-tetrazolium (MTT) assay. Cell cycle and apoptosis assay were determined by flow cytometry. TA-1 functions as an anticancer agent by triggering apoptosis potentiated by chemotherapeutic agents and TNF in human myeloid leukemia cells (KBM5) through a mechanism involving poly(ADP-ribose) polymerase (PARP) cleavage and initiator and effector caspases activation. Moreover, electrophoretic mobility shift assay (EMSA) revealed that TA-1 downregulated nuclear localization of NF-kappa B and its phosphorylation induced by TNF-alpha and this, allows the suppression of the degradation and phosphorylation of I kappa B and the inhibition of the phosphorylation of p65 phosphorylation and the p50-p65 heterodimer nuclear translocation, causing attenuation of NF-kappa B-regulated antiapoptotic (Survivin, Bcl-2, c-IAP1/2, Bcl-xL, Mcl-1, and cFLIP), invasion (ICAM1), metasatsis (MMP-9), and angiogenesis (VEGF) gene expression in KBM5; and finally reporter gene expression. Furthermore, treatment with essential oil and TNF-alpha suppressed the NF-kappa B DNA binding activity. Finally, the activation of nuclear factor-kappa B induced by different plasmids (TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKK beta) was inhibited following treatment with TA-1. Overall, TA-1 inhibits NF-kappa B activation and further growth and proliferation of cancer cells.