Talhouk Rabih S, Nasr Bilal, Fares Mohamed-Bilal, Ajeeb Bushra, Nahhas Rana, Al Aaraj Lamis, Talhouk Salma N, Ghaddar Tarek H, Saliba Najat A
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon ; Nature Conservation Center (NCC), American University of Beirut, Beirut 1107 2020, Lebanon.
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon ; Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Evid Based Complement Alternat Med. 2015;2015:474597. doi: 10.1155/2015/474597. Epub 2015 May 19.
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.
通过“生物活性导向分级分离”从东地中海地区特有的植物叙利亚科塔（Cota palaestina subsp. syriaca）中分离出一种倍半萜内酯1-β,10-环氧-6-羟基-1,10H-土木香内酯（K100）。K100可抑制内毒素（ET）诱导的正常小鼠乳腺SCp2细胞中的促炎标志物：白细胞介素-6（IL-6）、基质金属蛋白酶-9（MMP-9）和一氧化氮（NO）。计算机模拟分子对接表明，K100与抗癌化合物小白菊内酯（PTL）结构高度相似，可在相似位置以相当的结合亲和力结合PTL靶蛋白。K100和PTL这两种化合物均抑制二维培养的乳腺腺癌MDA-MB-231细胞的增殖并延长其细胞周期的S期。K100和PTL的无细胞毒性浓度降低了MDA-MB-231细胞的增殖率，并使其在三维培养中的形态从星状转变为球形集落。这伴随着小集落数量的显著增加和大集落数量的减少。此外，K100和PTL降低了MDA-MB-231细胞的细胞运动性和侵袭性。总之，这些结果表明K100具有与PTL类似的抗炎、抑制细胞生长和抗转移作用。
