title: C/EBPβ and CHOP participate in tanshinone IIA-induced differentiation and apoptosis of acute promyelocytic leukemia cells in vitro.
abstract: Our studies indicated that Tanshinone IIA (TanIIA), which is widely applied in the treatment of cardiovascular diseases with a rare occurrence of side effects, could promote APL cell differentiation and apoptosis. We found TanIIA induced the differentiation of NB4 and MR2 cells with elevated C/EBPβ and CHOP. When C/EBPβ was overexpressed in NB4 cells, the level of CD11b in the transfected cells was significantly elevated. When we used CHOP siRNA to suppress CHOP expression in NB4 cells and then treated these cells with a high concentration of TanIIA, the differentiation and apoptosis of these cells were both significantly increased. These data demonstrate that C/EBPβ is critical for APL cell differentiation and apoptosis induced by TanIIA, and that CHOP acts as a negative regulator of C/EBPβ activity. Our study suggested that TanIIA is a promising drug for treating newly diagnosed and ATRA-resistant APL, and a high concentration of TanIIA associated with inhibition of CHOP, maybe a potentially promising therapy strategy.
authors.affiliation: Department of Hematology, West China Medical School, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Kaiji
authors.initials: K
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Wentong
authors.initials: W
authors.lastname: Meng
authors.forename: Hongyun
authors.initials: H
authors.lastname: Xing
authors.forename: Yiming
authors.initials: Y
authors.lastname: Yang
mesh_terms: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C497249:DDIT3 protein, human; D010616:Phenanthrenes; C021751:tanshinone; D051742:Transcription Factor CHOP