Abstract
A sesquiterpene lactone 1-β,10-Epoxy-6-hydroxy-1,10H-inunolide (K100) was isolated through “bioassay-guided fractionation” from Cota palaestina subsp. syriaca, an Eastern Mediterranean endemic plant. K100 inhibited endotoxin- (ET-) induced proinflammatory markers: IL-6, MMP-9, and NO in normal mouse mammary SCp2 Cells. Molecular docking in silico suggested that K100, having highly analogous structure as parthenolide (PTL), an anticancer compound, could bind PTL target proteins at similar positions and with comparable binding affinities. Both compounds, K100 and PTL, inhibited the proliferation and prolonged the S-phase of the cell cycle of breast adenocarcinoma MDA-MB-231 cells grown in 2D cultures. Noncytotoxic concentrations of K100 and PTL decreased the proliferation rate of MDA-MB-231 and shifted their morphology from stellate to spherical colonies in 3D cultures. This was accompanied with a significant increase in the amount of small colonies and a decrease in the amount of large colonies. Moreover, K100 and PTL decreased cellular motility and invasiveness of MDA-MB-231 cells. In summary, these results suggest that K100 exhibits PTL-analogous anti-inflammatory, cytostatic, and antimetastatic effects.
Highlights
Cota palaestina DC, a plant endemic to Lebanon known in Arabic as “Bahar ghishai,” belongs to the Anthemideae tribe of the Asteraceae (Compositae) family, which comprises 25,000 species within three subfamilies and 17 tribes [1], many of which are employed in a variety of medicinal applications
Known as Cota palaestina spp. syriaca after the recognition of Cota as an independent genus [18,19,20], was selected for further study among 27 other indigenous Lebanese wild plant species that have been commonly used in Lebanese folk medicine [5]
The leaves are oblong in outline; its peduncles are long not thickened
Summary
Cota palaestina DC, a plant endemic to Lebanon known in Arabic as “Bahar ghishai,” belongs to the Anthemideae tribe of the Asteraceae (Compositae) family, which comprises 25,000 species within three subfamilies and 17 tribes [1], many of which are employed in a variety of medicinal applications. The extensively studied SL extracted from the plant T. parthenium “PTL” has been reported to exhibit antiproliferative activities upon binding and inhibiting the function of members of the NFκB, JAKSTAT, and TNFα signaling pathways [15]. Through bioactivity-guided fractionation of the water extract of Cota palaestina, this study attributes antiinflammatory and cytostatic activities of this plant to the parthenolide like sesquiterpene lactone 1-β,10-α-Epoxy-6αhydroxy-1,10H-inunolide (referred to hereafter as K100). This compound reduces inflammatory mediators interleukin-6 (IL-6), nitric oxide (NO), and matrix metalloproteinase-9 (MMP-9) production by endotoxin- (ET-) treated mammary epithelial cells (SCp2), a culture system previously reported as effective in screening for anti-inflammatory bioactive molecules [17]. The cytostatic activity is attributed to the ability of K100, to PTL, to partially revert growth phenotype, invasion, and motility of MDA-MB-231 breast adenocarcinoma cells
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