Comparative effects of parthenolide and a sesquiterpene lactone from Cota palaestina subsp. syriaca on tumor phenotype of MDA-MB-231 breast adenocarcinoma cells.

Abstract

Sesquiterpene lactones (SLs) constitute a large and a diverse group of biologically active plant compounds that possess anti-inflammatory and antitumor activities. Parthenolide (PTL) is the major SL and the primary compound responsible for the bioactivities of feverfew (Tanacetum parthenium). K100, an anti-inflammatory sesquiterpene lactone isolated through bioactive guided fractionation from cota Palestina subsp.syriaca,an Eastern Mediterranean endemic plant known in Arabic as ‘Bahar ghishai’, is analogous to the feverfew-extracted PTL known to inhibit proliferation and apoptosis in many human cancer cell lines.K100 Inhibited Endotoxin(ET)-induced pro-inflammatory markers: IL-6, MMP9 and NO in normal mouse mammary SCp2 Cells. Molecular docking in silico of one K100 isomer and DMAPT against several target proteins of PTL predicted that K100 can bind at similar positions as PTL, and with comparable binding affinities. K100 and PTL inhibited the proliferation and prolonged the S phase of the cell cycle of breast adenocarcinoma MDA-MB-231cells in 2D cultures. Non-cytotoxic concentrations of K100 and PTL decreased the proliferation rate of MDA-MB-231 and shifted their morphology from stellate into spherical accompaniedwith a significant increase in the amount of small colonies and a decrease in the amount of large colonies in 3D cultures. Moreover, K100 and PTL decreased cellular motility and invasiveness of MDA-MB-231 cells. Also, K100 and PTLup-regulated the levels of cadherins under 2Dculture conditionsand did not affect the total levels of MMP9 and P65. In summary, these results suggest that K100 exhibit PTL-analogous anti-inflammatory, anti-proliferative and anti-metastatic effects.