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Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells.
- Source :
-
Blood [Blood] 2013 May 02; Vol. 121 (18), pp. 3682-91. Date of Electronic Publication: 2013 Mar 13. - Publication Year :
- 2013
-
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.
- Subjects :
- Active Transport, Cell Nucleus drug effects
Active Transport, Cell Nucleus genetics
Animals
Antineoplastic Agents pharmacology
Cell Differentiation genetics
Cell Nucleus drug effects
Cell Nucleus metabolism
Gene Expression Regulation, Leukemic drug effects
HL-60 Cells
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Mice, SCID
Phospholipid Transfer Proteins genetics
Protein Transport drug effects
Protein Transport genetics
Tissue Distribution drug effects
U937 Cells
Xenograft Model Antitumor Assays
Cell Cycle Checkpoints drug effects
Cell Differentiation drug effects
Flavanones pharmacology
Glucosides pharmacology
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute metabolism
Leukemia, Myeloid, Acute pathology
Phospholipid Transfer Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 121
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 23487022
- Full Text :
- https://doi.org/10.1182/blood-2012-11-466219