title: Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic initiation factor 4E.
abstract: Cryptotanshinone (CPT), a diterpene quinone isolated from Salvia miltiorrhiza, is recently reported to have obvious anticancer activities against diverse cancer cells. However, the effect and regulatory mechanism of CPT remain unclear in human chronic myeloid leukemia (CML) cells. In this study, we investigated the antiproliferative activity of CPT on the multidrug resistant CML cells K562/ADM. Our results demonstrated that CPT decreased the cell viability of K562/ADM cells by inducing cell cycle arrest and apoptosis through suppressing the expression of cyclin D1 and Bcl-2. Further studies indicated that CPT mainly functions at post-transcriptional levels, suggesting the involvement of eukaryotic initiation factor 4E (eIF4E). CPT significantly reduced the expression and activity of eIF4E in K562/ADM cells. Overexpression of eIF4E obvious conferred resistance to the CPT antiproliferation and proapoptotic activity as well as the cyclin D1 and Bcl-2 expressions. Knockdown of eIF4E significantly reduced the inhibitory effect of CPT in K562/ADM, confirming the participation of eIF4E during CPT function process. More importantly, the relative inhibitory efficiency of CPT positively correlated with the reductions on eIF4E in primary CML specimens. These results demonstrated that CPT played antitumor roles in K562/ADM cells by inhibiting the eIF4E regulatory system. Our results provide a novel anticancer mechanism of CPT in human CML cells.
authors.affiliation: Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Ge
authors.forename: Rubin
authors.initials: R
authors.lastname: Cheng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jianping
authors.initials: J
authors.lastname: Shen
authors.forename: Laijun
authors.initials: L
authors.lastname: Peng
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.forename: Qun
authors.initials: Q
authors.lastname: Dai
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Haibing
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Ma
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects* / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1; C037886:cryptotanshinone