Effects of indirubin derivatives on the FLT3 activity and growth of acute myeloid leukemia cell lines
Indirubin is an active constituent of traditional Chinese preparations used for the treatment of chronic myelocytic leukemia (CML). In the present study, the inhibitory activity of indirubin and its derivatives toward Fms‐like tyrosine kinase 3 (FLT3) was examined. Indirubin‐3′‐oxime (IO) and 6‐brom...
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Published in | Drug development research Vol. 71; no. 4; pp. 221 - 227 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.06.2010
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Subjects | |
Online Access | Get full text |
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Summary: | Indirubin is an active constituent of traditional Chinese preparations used for the treatment of chronic myelocytic leukemia (CML). In the present study, the inhibitory activity of indirubin and its derivatives toward Fms‐like tyrosine kinase 3 (FLT3) was examined. Indirubin‐3′‐oxime (IO) and 6‐bromoindirubin‐3′‐oxime (BIO) had potent inhibitory activity against FLT3 (IC50=79 nM and 254 nM, respectively). We also tested the cytotoxicity of these compounds against acute myeloid leukemia cell lines: MV4;11 cells harboring a constitutively activated form of FLT3, and RS4;11 cells with wild‐type FLT3. IO and BIO potently inhibited the growth of MV4;11 cells with IC50 values of 30 nM and 61 nM, respectively. Conversely, RS4;11 cells were far less sensitive to these compounds. IO arrested the cell cycle of MV4;11 cells at the G1 phase, and increased the dead cell population at the sub‐G1 phase and annexin V‐positive cells. From these results, derivatives of IO may have potential to be developed as anti‐leukemic agents. Drug Dev Res 71: 221–227, 2010. © 2010 Wiley‐Liss, Inc. |
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Bibliography: | Korea Research Institute of Chemical Technology ark:/67375/WNG-9D8Z926X-J istex:4796047A116D1052252FAA961E398A22B8DA6536 Ministry of Education, Science and Technology ArticleID:DDR20363 |
ISSN: | 0272-4391 1098-2299 |
DOI: | 10.1002/ddr.20363 |