Jan M. Tuescher
Natural Product Laboratory, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB, Canada T1K 3M4
Deserae Tailfeathers
Natural Product Laboratory, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB, Canada T1K 3M4
Sophie M. Kernéis
Microbiology Research Group, 3000 College Dr S, Lethbridge College, Lethbridge, AB Canada T1K 1L6
Blandine Baratte
Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France; Sorbonne Université, CNRS, FR 2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Sandrine Ruchaud
Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France; Sorbonne Université, CNRS, FR 2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Stéphane Bach
Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France; Sorbonne Université, CNRS, FR 2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Muriel Batut
Pierre Fabre Laboratories, USR 3388 CNRS-Pierre Fabre, 3 avenue Hubert Curien, BP 13562, Toulouse, Cedex 1, France
Isabelle Pouny
Pierre Fabre Laboratories, USR 3388 CNRS-Pierre Fabre, 3 avenue Hubert Curien, BP 13562, Toulouse, Cedex 1, France
François Sautel
Pierre Fabre Laboratories, USR 3388 CNRS-Pierre Fabre, 3 avenue Hubert Curien, BP 13562, Toulouse, Cedex 1, France
Roy M. Golsteyn
Natural Product Laboratory, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB, Canada T1K 3M4
https://orcid.org/0000-0002-0251-7025
Keywords
Cell cycle; CETSA (cellular thermal shift assay); Kinase inhibitor; Natural products
Abstract
Introduction: Plant species within the prairie ecological zone of Canada are a source of natural products with important bio-activities. Investigation of these plants and the secondary metabolites that they produce will provide insight into their biology, and identify sources of natural products that may become new medicines or scientific tools.
Methods: We investigated a G1 phase arrest activity in extracts from the prairie plant, Thermopsis rhombifolia (Buffalo bean) by biology-guided fractionation and isolated luteolin. Cell based assays and CETSA were used to identify a cyclin-dependent kinase 9 inhibitory activity.
Results and Discussion: Luteolin treated cells showed decreased phosphorylation of the carboxy terminal domain of RNA polymerase II, and low levels of Mcl-1. Plant extracts or luteolin inhibited Cdk9 (cyclin dependent kinase) in tests in vitro, stabilized Cdk9 as determined by the cellular thermal shift assay (CETSA), and arrested cells in the G1 phase of the cell cycle.
Conclusions: Luteolin joins an increasing number of flavonoid inhibitors that make convenient cell biology tools and contribute to our understanding of natural product biology in plants.
Abstract