Isolation of a natural product with anti-mitotic activity from a toxic Canadian prairie plant.
| Autor: | Molina L; Natural Product and Cancer Cell Laboratories, University of Lethbridge, Lethbridge, AB, T1K 3M4 Canada., Williams DE; Department of Earth, Ocean, Atmospheric Sciences, University of British Columbia, Vancouver, BC, V6T 1Z4 Canada., Andersen RJ; Department of Earth, Ocean, Atmospheric Sciences, University of British Columbia, Vancouver, BC, V6T 1Z4 Canada., Golsteyn RM; Natural Product and Cancer Cell Laboratories, University of Lethbridge, Lethbridge, AB, T1K 3M4 Canada. |
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| Jazyk: | angličtina |
| Zdroj: | Heliyon [Heliyon] 2021 May 24; Vol. 7 (5), pp. e07131. Date of Electronic Publication: 2021 May 24 (Print Publication: 2021). |
| DOI: | 10.1016/j.heliyon.2021.e07131 |
| Abstrakt: | 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. Competing Interests: The authors declare no conflict of interest. (© 2021 The Authors. Published by Elsevier Ltd.) |
| Databáze: | MEDLINE |
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