title: Wogonin induced differentiation and G1 phase arrest of human U-937 leukemia cells via PKCdelta phosphorylation.
abstract: Wogonin, a natural monoflavonoid, has been shown to have tumor therapeutic potential in vitro and in vivo. Recently many studies have focused on the induction of apoptosis of tumor cells by wogonin. In this study, we found that wogonin could induce differentiation and G1 phase arrest of human U-937 leukemia cells. The growth of U-937 cells incubated with wogonin was inhibited in a time- and concentration-dependent manner. After treatment with wogonin, U-937 cells exhibited the characteristics of mature granulocytes, such as increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, membrane ruffling, a higher NBT-reducing ability, and an increased expression of CD11b. Moreover, wogonin could induce G1 phase arrest and influenced the expression of associated proteins. For example, the expression of phorsphorylated protein kinase C (PKC) delta, p21 increased, while that of cyclin D1/cyclin-dependent kinase (CDK) 4, p-Rb decreased. The upregulation of p21 could be reversed by rottlerin, an inhibitor of PKCdelta. Taken together, wogonin induced U-937 cells to undergo granulocytic differentiation and G1 phase arrest via PKCdelta phosphorylation-induced upregulation of p21 proteins.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Qiang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiao-Tang
authors.initials: XT
authors.lastname: Wang
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D044950:Flavanones; D051745:Protein Kinase C-delta; C085514:wogonin