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 - 14/11/17
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Abstract |
Teucrium alopecurus is an endemic plant limited to southern Tunisia. In the present study, the chemical composition, anticancer and nuclear factor-κB (NF-κB) 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 α-Bisabolol, (+)-epi-Bicyclosesquiphellandrene and α-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-κB and its phosphorylation induced by TNF-α and this, allows the suppression of the degradation and phosphorylation of IκB and the inhibition of the phosphorylation of p65 phosphorylation and the p50-p65 heterodimer nuclear translocation, causing attenuation of NF-κB-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-α suppressed the NF-κB DNA binding activity. Finally, the activation of nuclear factor-κB induced by different plasmids (TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKβ) was inhibited following treatment with TA-1. Overall, TA-1 inhibits NF-κB activation and further growth and proliferation of cancer cells.
Le texte complet de cet article est disponible en PDF.Abbreviations : BSA, FBS, PBS-T, SDS-PAGE, 5-FU, DMEM, Bcl-2, BcL-xL, c-FLIP, cyclin D1, IκBα, ICAM1, IMDM, IKK, Mcl-1, MMP-9, TNF, TRAF, cIAP1/2, p65, RPMI 1640, SDS, SEAP, TNFR, VEGF, XIAP
Keywords : TA-1, NF-κB, Human myeloid leukemia, Metastasis
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Vol 95
P. 1876-1885 - novembre 2017 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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