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Logo of bmcamBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Complementary and Alternative Medicine
BMC Complement Altern Med. 2012; 12: 89.
Published online Jul 9, 2012. doi:  10.1186/1472-6882-12-89
PMCID: PMC3439278
Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells
Melody Saikali,1,2,3 Akram Ghantous,2,3 Racha Halawi,4 Salma N Talhouk,3,5 Najat A Saliba,3,6 and Nadine Darwichecorresponding author1,2,3
1Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon
2Department of Biology, American University of Beirut, Beirut, Lebanon
3Ibsar, Nature Conservation Center for Sustainable Futures, American University of Beirut, Beirut, Lebanon
4Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
5Department of Landscape Design and Ecosystem Management, American University of Beirut, Beirut, Lebanon
6Department of Chemistry, American University of Beirut, Beirut, Lebanon
corresponding authorCorresponding author.
Melody Saikali: ms200/at/; Akram Ghantous: ayg01/at/; Racha Halawi: rzh04/at/; Salma N Talhouk: ntsalma/at/; Najat A Saliba: ns30/at/; Nadine Darwiche: nd03/at/
Received March 12, 2012; Accepted June 19, 2012.
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.
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.
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.
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.
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