Anti-mitotic activity of six Asteraceae plant extracts and identification of the sesquiterpene lactone hymenoratin from the Canadian plant Hymenoxys richardsonii

Abstract

In this thesis we investigate the anti-mitotic activity of six Canadian Asteraceae species. Three plant extracts arrested cancer cells in mitosis with different characteristics. Hymenoxys richardsonii extract induced a mitotic arrest measured by rounded cell morphology, phosphorylated histone H3, active Cdk1/Cyclin B, high levels of Plk1, and G2/M arrest by flow cytometry. Mitotic-arrested cells were characterized by chromosome congression failure, distorted mitotic spindles, and damaged DNA. Biology-guided fractionation led to the purification of the active compound hymenoratin, a sesquiterpene lactone closely related to pulchelloid A, which was isolated from the anti-mitotic plant Gaillardia aristata. This is the first time that H. richardsonii or hymenoratin is reported to elicit a biological activity on cancer cells. Investigation of the structure-activity relationship between sesquiterpene lactones and anti-mitotic activity is potentially useful to understand unknown biological mechanisms or to develop anticancer drug candidates.