The Canadian Prairie Plant Thermopsis rhombifolia Contains Luteolin, a Flavone that Inhibits Cyclin Dependent Kinase 9 and Arrest Cells in the G1-Phase of the Cell Cycle

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Jan M. Tuescher
Deserae Tailfeathers
Sophie M. Kernéis
Blandine Baratte
Sandrine Ruchaud
Stéphane Bach
Muriel Batut
Isabelle Pouny
François Sautel
Roy M. Golsteyn 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.

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