We are investigating plants from the prairie ecological zone of Canada to identify natural products that inhibit mitosis in cancer cells. Investigation of plant parts from the Canadian plant species Hymenoxys richardsonii (Asteraceae) revealed that leaf extracts (PP-360A) had anti-mitotic activity on human cancer cell lines. Cells treated with leaf extracts acquired a rounded morphology, similar to that of cells in mitosis. We demonstrated that the rounded cells contained mitotic spindles and phospho-histone H3 using the techniques of immunofluorescence microscopy. By biology-guided fractionation of H. richardsonii leaves, we isolated a sesquiterpene lactone named hymenoratin, which had not been previously assigned a biological activity. Cells treated with hymenoratin have phospho-histone H3 positive chromosomes, a mitotic spindle, and enter a prolonged mitotic arrest in which the spindles become distorted. By Western blot analysis, hymenoratin treated cells acquire high levels of cyclin B and dephosphorylated Cdk1. There is a growing body of evidence that select members of the sesquiterpene lactone chemical family have anti-mitotic activity.
Natural products from plants in Canadian ecological zones are understudied. There are, however, sound scientific arguments to justify investigation of natural products from plant species found within these zones. We review a broad range of scientific and local literature describing the features of the Canadian prairie ecological zone and the Asteraceae taxonomical family. Species from Asteraceae are well represented in the prairie ecological system, although very few have been investigated for natural products with bio-medical properties. Data from a range of sources that address ecological interactions, abiotic features, and Traditional Knowledge provide a foundation for future scientific studies of plant natural products found within Canadian borders. We draw from discoveries of the Asteraceae family and one of its major classes of secondary metabolites, sesquiterpenes, to stimulate research of Asteraceae species in Canada.
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