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

Biomed Pharmacother. 2017 Nov:95:1876-1885. doi: 10.1016/j.biopha.2017.09.115. Epub 2017 Oct 6.


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.

Keywords: Human myeloid leukemia; Metastasis; NF-κB; TA-1.

MeSH terms

  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Flow Cytometry
  • Gas Chromatography-Mass Spectrometry
  • Gene Expression Regulation / drug effects
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / metabolism
  • Leukemia, Myeloid / drug therapy
  • NF-kappa B / metabolism
  • Oils, Volatile / isolation & purification
  • Oils, Volatile / pharmacology*
  • Plant Leaves
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*
  • Teucrium / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tunisia


  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • Oils, Volatile
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase