Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells

Abstract

BackgroundSesquiterpene 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.MethodsThe 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.Resultsβ-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.ConclusionsThese 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.

Prolonged overexpression of Wnt10b induces epidermal keratinocyte transformation through activating EGF pathway

“…The neoplasm was formed at about day 15 after prolonged Wnt10b induction, which is in similar duration to JB6P+ cell transformation under ectopic stimuli (Su et al 2014). While different from JB6P+ cell clustering induced by TPA, EGF, or TNF-a signaling, which showed simple cell aggregation in previous studies (Saikali et al 2012; Han et al 2011; Su et al 2014), the colonies observed in the present study were totally newly induced. Also, the cell colony displayed obvious boarder to the surrounding cells, which were not transformed.…”

Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells

“…Conversely, several reports indicate that UA remarkably reduces oxidative stress and increases the activity of antioxidant enzymes [49-51]. We observed that the expression of HO-1 (antioxidant), NQO1, and UGT1A1 (detoxification) noticeably increased at both the mRNA and protein levels in the JB6 P+ cells treated with UA; however, TPA activated AP-1, NF-κB, and ERK 1/2 as well [43, 52]. Moreover, UA targets AP-1, NF-κB, and ERK 1/2 [2].…”

Phytochemical Study and the Antiproliferative Activity of Inula Vulgaris Species Grown in Lebanon

“…On CaCo2, the IC50 of I. vis was 12µg/ml in the Trypan blue assay and 22µg/ml by the MTT test, indicating high potency. Since the IC50 of the extracts were less than 30µg/ml, this coincides with the American National Cancer Institute, which specified definite criteria for cytotoxic activity of plant extracts at IC50 less than 30 µg/ml [22]. Insignificant differences were observed among the two studied plants for each of the cells that were evaluated, which indicates comparable potencies.…”