title: Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl-JAK/STAT Signaling Pathways.
abstract: This study evaluates the anticancer effects of dehydrocostus lactone, a plant-derived sesquiterpene lactone, on human chronic myeloid leukemia cells. Dehydrocostus lactone significantly inhibits cell proliferation by inducing cells to undergo cell cycle arrest, apoptosis, and differentiation. Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK1) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells. Dehydrocostus lactone also induces apoptosis by increasing the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (MMP), and modulating the protein levels of Bcl-2 family members. We also found that dehydrocostus lactone significantly inhibits the phosphorylation expression of Bcr/Abl, STAT5, JAK2, and STAT3 and downstream molecules including p-CrkL, Mcl-1, Bcl-XL, and Bcl-2 proteins in K562 cells. At a low concentration, dehydrocostus lactone significantly increased CD11b and CD14 expression on the surface of K562 cells, and induced cells to differentiate into monocytes or mature macrophages. Taken together, this study provides new insight into the molecular mechanisms of dehydrocostus lactone actions that may contribute to the chemoprevention of chronic myeloid leukemia. J. Cell. Biochem. 118: 3381-3390, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, 116023, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of China Medical University, Shenyang, 110004, P.R. China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Qin
authors.affiliation: Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, 116023, P.R. China.
authors.forename: Chunhui
authors.identifier: 0000-0003-1597-8469
authors.initials: C
authors.lastname: Yang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D007783:Lactones / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D007783:Lactones; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D012717:Sesquiterpenes; C083030:dehydrocostus lactone; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr
keywords: Bcr/Abl; CHRONIC MYELOID LEUKEMIA; DEHYDROCOSTUS LACTONE; STAT PROLIFERATION