Reference - Detail
|Author||Aoki S, Kong D, Matsui K, Kobayashi M.|
|Title||Smenospongine, a spongean sesquiterpene aminoquinone, induces erythroid differentiation in K562 cells.|
The differentiation of K562 chronic myelogenous leukemia (CML) cells by smenospongine, which is a sesquiterpene aminoquinone isolated from a marine sponge, was examined. Smenospongine increased hemoglobin production in K562 cells at concentrations of 3-15 microM. In addition, flow cytometric analysis of smenospongine-treated K562 cells with FITC-labeled glycophorin A antibody showed an increase of glycophorin A expression, a marker for erythroid differentiation. Cell-cycle analysis showed G1 arrest in K562 cells after treatment with smenospongine for 24 h. The effect on expression of CIP/KIP family cyclin-dependent kinase inhibitors was investigated by Western blotting analysis and the result showed increased expression of p21, which is known to play an important role in differentiation. Furthermore, smenospongine was also found to inhibit the phosphorylation of Crkl, a substrate of Bcr-Abl tyrosine kinase, which is known as a causative protein of CML. In conclusion, our investigation indicated that smenospongine induced the differentiation of K562 cells into erythroblasts along with cell-cycle arrest at G1 phase and the mechanism might be attributed to the increased expression of p21.
|MeSH||Adaptor Proteins, Signal Transducing* Animals Antineoplastic Agents / chemistry Antineoplastic Agents / isolation & purification Antineoplastic Agents / pharmacology* Blotting, Western Cell Differentiation / drug effects* Erythroid Cells / cytology Erythroid Cells / drug effects* Flow Cytometry Fluorescein-5-isothiocyanate Glycophorin / biosynthesis Hemoglobins / biosynthesis Humans Indonesia K562 Cells Leukemia, Myelogenous, Chronic, BCR-ABL Positive Nuclear Proteins / metabolism Phosphorylation Porifera / chemistry* Quinones / chemistry* Quinones / isolation & purification Quinones / pharmacology* Sesquiterpenes / chemistry* Sesquiterpenes / isolation & purification Sesquiterpenes / pharmacology*|
|WOS Category||PHARMACOLOGY & PHARMACY ONCOLOGY|
|Human and Animal Cells|