Isolation of novel natural products with distinct anti-mitotic activities from the Canadian plant Arnica cordifolia

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dc.contributor.authorLockwood, Tanner C.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorGolsteyn, Roy
dc.date.accessioned2024-09-26T20:43:22Z
dc.date.available2024-09-26T20:43:22Z
dc.date.issued2024
dc.degree.levelMasters
dc.description.abstractThis thesis investigates anti-mitotic natural products isolated from Arnica cordifolia (heartleaf arnica), a Canadian plant species. Extracts prepared from A. cordifolia induced mitotic arrest without affecting mitotic spindle morphology, a phenotype unlike that of any mitotic inhibitor previously identified by our laboratory. By investigating this unique phenotype, we identified five anti-mitotic sesquiterpene lactones from A. cordifolia using biology-guided fractionation: three novel structures, and the known compounds aromaticin and pulchellin-2α-O-isovalerate. These compounds induced mitotic arrest with distinct effects on mitotic spindle morphology. Investigation into potential target pathways revealed that aromaticin treatment induced ubiquitin foci formation in cancer cells, suggesting that it may affect the ubiquitin-proteasome pathway. This is the first report of three novel mitotic inhibitors, of the anti-mitotic effects of pulchellin-2α-O-isovalerate, and of the anti-mitotic and ubiquitin-altering effects of aromaticin. Differences in the structures and biological activities of these anti-mitotic sesquiterpene lactones suggest they act by distinct cellular targets and mechanisms of action. The discovery of mitotic inhibitors from Canadian plant species and other underexplored sources of natural products expands our understanding of mitosis, and these compounds may have applications in research or therapy.
dc.embargoNo
dc.identifier.urihttps://hdl.handle.net/10133/6917
dc.language.isoen
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences
dc.publisher.departmentDepartment of Biological Sciences
dc.publisher.facultyArts and Science
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)
dc.subjectnatural products
dc.subjectCanadian prairie plants
dc.subjectmitosis
dc.subjectmitotic arrest
dc.subjectmitotic regulation
dc.subjectmitotic spindle
dc.subjectcell division inhibitors
dc.subjectsesquiterpene lactones
dc.subject.lcshDissertations, Academic
dc.subject.lcshNatural products--Analysis
dc.subject.lcshPrairie plants--Research--Alberta
dc.subject.lcshMitosis--Regulation--Research
dc.subject.lcshSpindle (Cell division)--Research
dc.subject.lcshSesquiterpene lactones--Research
dc.subject.lcshArnica--Research
dc.titleIsolation of novel natural products with distinct anti-mitotic activities from the Canadian plant Arnica cordifolia
dc.typeThesis
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