title: Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.
abstract: BACKGROUND
  Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-β-methoxy-iso-seco-tanapartholide (β-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how β-tan and Sal A modulate their signaling pathways in JB6P + cells.
  
  
  METHODS
  The effects of β-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes.
  
  
  RESULTS
  β-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways.
  
  
  CONCLUSIONS
  These results highlight the anti-tumor promoting properties of β-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary medicine practices.
authors: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
authors: Melody
authors: M
authors: Saikali
authors: Akram
authors: A
authors: Ghantous
authors: Racha
authors: R
authors: Halawi
authors: Salma N
authors: SN
authors: Talhouk
authors: Najat A
authors: NA
authors: Saliba
authors: Nadine
authors: N
authors: Darwiche
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D031179:Centaurea / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008877:Middle East; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: C576547:3-beta-methoxy-iso-seco-tanapartholide; D016588:Anticarcinogenic Agents; D006575:Heterocyclic Compounds, 3-Ring; D007783:Lactones; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; C528991:salograviolide A