Prairie to Pharmacy Research Program: Investigation of Prairie Plants for Chemicals that Inhibit Vital Cellular Pathways

The prairie ecological zone harbours plants that flourish under the selective pressures of a short growing season and large grazing herbivores. These features induce plants to produce secondary metabolites that are toxic to mammals. Evidence from agricultural sources supports the hypothesis that these plants contain chemicals that will be toxic to human cells. We have prepared a unique extract library from prairie plants representing 18 taxonomical families. The majority of extracts in the library are toxic to cancer cells at concentrations ranging from 15 to 150µg/mL. A key component of our research is to use cell-based phenotypic assays to investigate precisely how the extracts or chemicals affect cells. We have identified an anti-mitotic activity in extracts from 5 species of the taxonomical family Asteraceae. Extracts PP-006 and PP-360 induced mitotic cell rounding characterized by high Cdk1 enzyme activity, a metaphase arrangement of chromosomes, followed by a striking distortion of the mitotic spindle and damaged chromosomes. By biology-guided fractionation of extracts, we isolated the natural product Pulchelloid A and four other sesquiterpenes that have anti-mitotic activity. Of the 3000 described sesquiterpenes, only 6 have a mitotic arrest activity. With extract PP-630 from the family Caprifoliaceae, we have observed an unusual cellular phenomenon in which treated cells acquire a large perinuclear vacuole. To date, the perinuclear region of cells is poorly described in structure and components. Finally, we have identified a pro-apoptotic activity from a flavone isolated from the Buffalo bean (Fabaceae). Our analysis indicates that prairie plants are a rich source of chemicals for use as tools to investigate cell function, and potential cancer treatments.