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
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