Isolation of a natural product with anti-mitotic activity from a toxic Canadian prairie plant

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.

Automated summary

The investigation found a new sesquiterpene lactone named hymenoratin from the plant Hymenoxys richardsonii in the prairie ecological zone of Canada, exhibiting anti-mitotic activity against cancer cells and causing prolonged mitotic arrest. Treatment with hymenoratin led to high levels of cyclin B and dephosphorylated Cdk1 in cells, indicating potential as a novel anti-cancer compound in the sesquiterpene lactone chemical family.