ReferenceID 406
PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells induced by wogonoside
Cell Death Dis
Multiple lines of evidence have demonstrated that increased expression of phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute myeloid leukemia (AML) cells by several differentiation-inducing ag
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Record Fields
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- Reference Id
- 406
- Evidence Id
- 16996
- Core Evidence Id
- 16996
- Source Reference Id
- 781
- Herb2 Reference Id
- HBREF001346
- Subject Paper Key
- HBIN048376_28492556
- Pubmed Id
- 28492556
- Doi
- 10.1038/cddis.2017.175
- Paper Title
- PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells induced by wogonoside
- Paper Abstract
- Multiple lines of evidence have demonstrated that increased expression of phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute myeloid leukemia (AML) cells by several differentiation-inducing agents including ATRA and phorbol 12-myristate 13-acetate. However, none of these agents can achieve nonhomogenous subcellular distribution of PLSCR1. We have demonstrated that wogonoside possesses differentiation and anti-leukemic effects in AML cell lines by promoting PLSCR1 trafficking into nucleus. Here we report that wogonoside promotes the expression of PLSCR1 and enhances its nuclear translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter in AML patient-derived primary cells. Wogonoside activates IP3R1, in turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads to cell differentiation. Our in vivo study further confirms that wogonoside can promote PLSCR1 and IP3R1 expression in primary AML cells and reduce the AML cell counts in engrafted nonobese diabetic/severe combined immunodeficient mice. Taken together, our findings provide new insight into the mechanism of wogonoside-induced differentiation and anti-leukemic effect on primary AML cells, suggesting the therapeutic potential of wogonoside for AML, especially for non-APL AML.
- Journal
- Cell Death Dis
- Publish Year
- 2017
- Experiment Subject
- aml cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Acute Myeloid Leukemia; Leukemia
- Paper Title Cn
- Paper Title En
- PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells induced by wogonoside
- Bilingual Status
- semi_complete