Natural Product Laboratory, University of Lethbridge, 4401 University Drive W, Lethbridge, AB T1K 3M4, Canada.
Departments of Chemistry and EOAS, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z6, Canada.
Fitoterapia. 2024 Sep;177:106075. doi: 10.1016/j.fitote.2024.106075. Epub 2024 Jun 17.
The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most phylogenetically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.
加拿大草原生态系统受到非生物和生物条件的影响,促使植物产生次生代谢物,从而影响哺乳动物的生理机能。先前的研究表明,源自加拿大草原和山地科迪勒拉生态系统的某些植物物种的提取物对人类癌细胞系具有抗有丝分裂活性。在这项研究中,我们研究了冰川百合(Erythronium grandiflorum),它在进化上与菊科最为遥远,并且具有抗有丝分裂活性。当添加到细胞系中时,E. grandiflorum 提取物会诱导细胞呈现圆形形态,并使细胞停滞在细胞周期的 G2/M 期。显示出圆形表型的所有细胞均为磷酸组蛋白 H3 阳性,并包含扭曲的有丝分裂纺锤体。这种抗有丝分裂活性与先前从百合科分离出的化合物秋水仙碱不同。通过基于生物学的分级分离,我们分离出天然产物(+)-6-郁金香苷 A,并首次报道了其抗有丝分裂活性。这些结果揭示了次生代谢物中的化学结构,并扩展了具有抗有丝分裂活性的加拿大草原植物的范围,这些植物可能成为新的科学工具,或用于开发抗增殖药物。