Physcion 8-O-β-glucopyranoside exhibits anti-leukemic activity through targeting sphingolipid rheostat

Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in people younger than 20 years of age. This study was designed to explore the anti-leukemia activity of physcion 8-O-β-glucopyranoside (PG) in B-cell ALL. NALM6 and SupB15 cells were used as model cell lines. Cell viability, cell ap...

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Bibliographic Details
Published in:Pharmacological reports 2018-09, Vol.70 (5), p.853
Main Authors: Han, Jinyan, Zhao, Ping, Shao, Weiqin, Wang, Zengmin, Wang, Fengxue, Sheng, Lei
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Survival - drug effects
Emodin - analogs & derivatives
Emodin - pharmacology
Glucosides - pharmacology
Humans
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Sphingolipids - metabolism
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Summary:Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in people younger than 20 years of age. This study was designed to explore the anti-leukemia activity of physcion 8-O-β-glucopyranoside (PG) in B-cell ALL. NALM6 and SupB15 cells were used as model cell lines. Cell viability, cell apoptosis, cell cycle distribution were determined by CCK-8 assay, DNA fragmentation assay and flow cytometry, and flow cytometry, respectively. Expression of proteins involved in cell apoptosis and cell cycle regulation was determined by western blot and the levels of ceramide and sphingosine 1-phosphate (S1P) were determined by ELISA. Activity of sphingosine kinase 1 (SphK1) was also determined with a Sphingosine Kinase Assay Kit. In the present study, both model cell lines were transfected with siRNA targeting SphK1 or an overexpression plasmid to examine the role of SphK1 in the anti-leukemia activity of PG. Moreover, the efficacy of PG was examined in vivo in a mouse model by measuring survival and spleen weight. Our results provided experimental evidence that PG could significantly induce apoptosis and cell cycle arrest in vitro. Mechanistically, the anti-leukemia activity of PG was mediated by its ability to repress SphK1 and thus modulate ceramide-S1P rheostat. Moreover, the anti-leukemia activity of PG was also verified in a murine model. Collectively, our results indicate that PG may be a promising agent for the treatment of B-cell leukemia.
ISSN:1734-1140