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: Hai-Wei Zhang, Yong Yang, Kun Zhang, Lei Qiang, Li Yang, Lan Yang, Yang Hu, Xiao-Tang Wang, Qi-Dong You, Qing-Long Guo
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 591 Issue 1-3 Pg. 7-12 (Sep 04 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18577379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Flavanones
• Protein Kinase C-delta
• wogonin

Topics

• Cell Differentiation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Flavanones (administration & dosage, pharmacology)
• G1 Phase (drug effects)
• Humans
• Lymphoma, Large B-Cell, Diffuse (metabolism)
• Phosphorylation (drug effects)
• Protein Kinase C-delta (drug effects, metabolism)
• Time Factors
• U937 Cells
• Up-Regulation (drug effects)