Transcriptome analysis of K562 myeloid leukemia cells treated with butin, butein, and sulfuretin from the heartwood of Cotinus coggygria Scop.

Flavonoids are a long-known, promising class of active compounds with proven anticancer activity, but the exact effects of butin, butein, and sulfuretin, isolated from heartwood extracts of Cotinus coggygria Scop., in chronic myeloid leukemia K562 cells remain insufficiently defined. Flavonoids butin, butein, and sulfuretin showed cytotoxic activity against leukemia cells, but their mechanisms in K562 cells remain unknown. K562 cells were treated with extracts (ethanol, water, and methylene chloride/methanol) and compounds (butin, butein, and sulfuretin). Flow cytometry was used to determine cell cycle distribution and apoptosis activation after the treatment. Caspase inhibition was used to examine the cell death mode. Three independent mRNA-seq experiments were performed in K562 cells, followed by DGE analysis and pathway-level analyses using Reactome and KEGG GSEA, as well as network and pathway-cluster analyses. Transcriptome-wide analyses revealed overlapping, but compound-specific responses, with butein inducing the broadest transcriptional effect (809 DEGs), followed by butin (439 DEGs), and sulfuretin (299 DEGs), and 134 DEGs shared across all treatments. The transcriptomic profiles revealed compound-specific, partially overlapping responses. Butin treatment produced a transcriptional shift marked by suppression of RNA processing, mRNA splicing, translation initiation, and mitochondrial bioenergetics, including OXPHOS and TCA. Butein similarly induced coordinated downregulation of mitochondrial respiration, RNA maturation, mRNA maturation, and mRNA transport. Sulfuretin displayed a distinct pattern characterized by positive enrichment of stress, inflammatory, immune and proteasome-related pathways, alongside negative enrichment of RB1/E2F -associated G1/S transition programs. Investigation of the C. coggygria heartwood-derived flavonoids butin, butein, and sulfuretin indicates that these flavonoids promote transcriptomic reprogramming consistent with growth suppression, metabolic downshift, and activation of adaptive stress-response networks. These results provide a transcriptomic framework for further investigation of their antileukemic properties, which can be translated to other types of malignancy.