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Effects of indirubin derivatives on the FLT3 activity and growth of acute myeloid leukemia cell lines
Author(s) -
Han SunYoung,
Ahn Jin Hee,
Shin Chan Young,
Choi SangUn
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20363
Subject(s) - indirubin , myeloid leukemia , leukemia , chemistry , cell culture , pharmacology , cancer research , myeloid , biological activity , medicine , biology , biochemistry , in vitro , genetics , art , visual arts , indigo
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 (IC 50 =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 IC 50 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 G 1 phase, and increased the dead cell population at the sub‐G 1 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.