Costunolide promotes imatinib-induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl-Stat5 pathway

Costunolide, a sesquiterpene lactone, is a small molecular monomer extracted from Inula helenium (Compositae). In the present study, we assessed the antileukemia effects of costunolide on the human chronic myeloid leukemia cell line K562 and its combined activity with imatinib. A Cell Counting Kit-8 assay demonstrated that costunolide significantly inhibited K562 cell proliferation and enhanced imatinib-induced anti-proliferative activity. We found that costunolide significantly induced mitochondrial apoptosis in K562 cells by modulating the protein levels of Bcl-2 family members and by inducing caspase activation. Costunolide promoted imatinib-induced apoptosis via the Bcr/Abl-signal transducer and activator of transcription 5 pathway. Costunolide inhibited proliferation by inducing cell cycle arrest in the G₂ /M phase by decreasing cyclin B1 and cyclin-dependent kinase 2 expression and increasing p21 expression. Together, these results demonstrate that costunolide may be a potent therapeutic agent against chronic myeloid leukemia.