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.

Isolation of a natural product with anti-mitotic activity from a toxic Canadian prairie plant

“…We are investigating if plants in the prairie ecological zone of Canada contain natural products that inhibit mitosis or the cell cycle in cancer cells [8]. To understand better how a subgroup of sesquiterpene lactones induce mitotic arrest we investigated the Hymenoxys richardsonii species from the Asteraceae family [9].…”

Extracts Prepared from a Canadian Toxic Plant Induce Light-Dependent Perinuclear Vacuoles in Human Cells

“…We are investigating plants from the prairie ecological zone to discover new cell biology tools with which to study how human cells function. We have previously reported that extracts prepared from several prairie plant species, including Thermopsis rhombifolia that induced a cell cycle arrest identified by phenotypic assays [ 3 , 9 ]. Here, we identified extracts prepared from Symphoricarpos occidentalis (Caprifoliaceae) that induce a striking cellular phenotype when applied to human cells.…”