title: Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells.
abstract: Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the anticancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted antiproliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through the induction of G1 phase arrest and the promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle- and differentiation-related genes, including the upregulation of p21waf1/cip1 and downregulation of the oncogenic protein c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonoside-associated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Hui
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Yansu
authors.initials: Y
authors.lastname: Qin
authors.forename: Cong
authors.initials: C
authors.lastname: Gu
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D014018:Tissue Distribution / Q000187:drug effects; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D005960:Glucosides; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; C473995:wogonoside