Wogonin induced differentiation and G1 phase arrest of human U-937 leukemia cells via PKCdelta phosphorylation.
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.
Zhang
Hai-Wei
HW
Jiangsu Key Laboratory of Carcinogenesis and intervention, China Pharmaceutical University, Nanjing 210009, China.
Yang
Yong
Y
Zhang
Kun
K
Qiang
Lei
L
Yang
Li
L
Yang
Lan
L
Hu
Yang
Y
Wang
Xiao-Tang
XT
You
Qi-Dong
QD
Guo
Qing-Long
QL
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
D050759:Cyclin-Dependent Kinase Inhibitor p21; D044950:Flavanones; D051745:Protein Kinase C-delta; C085514:wogonin