Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins.

ABSTRACT: Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms (MPNs); however, a considerable number of patients respond suboptimally. Here, we evaluated the efficacy of micheliolide (MCL), a natural guaianolide sesquiterpene lactone, alone or in combination with ruxolitinib in samples from patients with MPNs, JAK2V617F-mutated MPN cell lines, and a Jak2V617F knock-in mouse model. MCL effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in vitro. Co-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib alone. Moreover, dimethylaminomicheliolide (DMAMCL), an orally available deriva

SUBMITTER: Huang H 

PROVIDER: S-EPMC10629731 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature