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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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October 2014 Volume 45 Issue 4

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

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International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

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Article

Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics

  • Authors:
    • Meng Huang
    • Hai-Shu Lin
    • Ying Shiuan Lee
    • Paul C. Ho
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore
  • Pages: 1724-1734
    |
    Published online on: July 21, 2014
       https://doi.org/10.3892/ijo.2014.2548
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Abstract

Meisoindigo has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia (CML) in China since the 1980s. In the present study, the in vitro antileukemic activity of meisoindigo was investigated in acute promyelocytic leukemia (APL) cells, acute myeloid leukemia (AML) cells, and myelomonocytic leukemia cells (NB4, NB4.007/6, HL-60 and U937) comprising both retinoic acid-sensitive and retinoic acid-resistant cells. We found that meisoindigo effectively inhibited the growth and/or proliferation of these four cell types at µM levels. The effects of meisoindigo in these cells are related to its proliferation inhibition and apoptosis induction, and are independent of cell cycle arrest, indicating that meisoindigo could be possible in the treatment of APL, AML and retinoic acid resistant APL. The in vivo pharmacokinetics of meisoindigo and its major circulatory metabolites in rat plasma were then investigated by a newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The profiles of plasma concentration versus time were plotted and the relevant pharmacokinetic parameters were calculated for meisoindigo and its reductive metabolites. The plasma concentrations of meisoindigo after oral administration were much lower than the in vitro IC50s determined in the leukemic cells. The contradicting poor pharmacokinetic characteristics and the established clinical efficacy of meisoindigo could indicate the presence of active metabolites in vivo.
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1 

Xiao Z, Qian L, Liu B and Hao Y: Meisoindigo for the treatment of chronic myelogenous leukaemia. Br J Haematol. 111:711–712. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Xiao Z, Hao Y, Liu B and Qian L: Indirubin and meisoindigo in the treatment of chronic myelogenous leukemia in China. Leuk Lymphoma. 43:1763–1768. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Ji XJ, Liu XM, Li K, Chen RH and Wang LG: Pharmacological studies of meisoindigo: absorption and mechanism of action. Biomed Environ Sci. 4:332–337. 1991.PubMed/NCBI

4 

Liu XM, Wang LG, Li HY and Ji XJ: Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo. Biochem Pharmacol. 51:1545–1551. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Xiao Z, Wang Y, Lu L, et al: Anti-angiogenesis effects of meisoindigo on chronic myelogenous leukemia in vitro. Leuk Res. 30:54–59. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Lee CC, Lin CP, Lee YL, Wang GC, Cheng YC and Liu HE: Meisoindigo is a promising agent with in vitro and in vivo activity against human acute myeloid leukemia. Leuk Lymphoma. 51:897–905. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F and Berger R: NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood. 77:1080–1086. 1991.PubMed/NCBI

8 

Breitman TR, Selonick SE and Collins SJ: Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA. 77:2936–2940. 1980. View Article : Google Scholar

9 

Dermime S, Grignani F, Rogaia D, Liberatore C, Marchesi E and Gambacorti-Passerini C: Acute promyelocytic leukaemia cells resistant to retinoic acid show further perturbation of the RAR alpha signal transduction system. Leuk Lymphoma. 16:289–295. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Olsson IL and Breitman TR: Induction of differentiation of the human histiocytic lymphoma cell line U-937 by retinoic acid and cyclic adenosine 3′:5′-monophosphate-inducing agents. Cancer Res. 42:3924–3927. 1982.

11 

Huang M, Goh LT and Ho PC: Identification of stereoisomeric metabolites of meisoindigo in rat liver microsomes by achiral and chiral liquid chromatography/tandem mass spectrometry. Drug Metab Dispos. 36:2171–2184. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Huang M and Ho PC: Identification of metabolites of meisoindigo in rat, pig and human liver microsomes by UFLC-MS/MS. Biochem Pharmacol. 77:1418–1428. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Huang M, Lee YS and Ho PC: Identification of circulatory and excretory metabolites of meisoindigo in rat plasma, urine and feces by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 24:729–741. 2010. View Article : Google Scholar

14 

Collins SJ, Gallo RC and Gallagher RE: Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 270:347–349. 1977. View Article : Google Scholar : PubMed/NCBI

15 

Sundstrom C and Nilsson K: Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 17:565–577. 1976. View Article : Google Scholar : PubMed/NCBI

16 

Song L and Qian L: Apoptosis inducing effect of meisoindigo on K562 cells. Zhongguo Zhong Xi Yi Jie He Za Zhi. 19:353–355. 1999.(In Chinese).

17 

Lin RJ, Egan DA and Evans RM: Molecular genetics of acute promyelocytic leukemia. Trends Genet. 15:179–184. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Bedner E, Li X, Gorczyca W, Melamed MR and Darzynkiewicz Z: Analysis of apoptosis by laser scanning cytometry. Cytometry. 35:181–195. 1999. View Article : Google Scholar

19 

Cohen GM, Sun XM, Snowden RT, Dinsdale D and Skilleter DN: Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J. 286:331–334. 1992.PubMed/NCBI

20 

Hoessel R, Leclerc S, Endicott JA, et al: Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. 1:60–67. 1999.PubMed/NCBI

21 

Huang M, Choo LW and Ho PC: Characterization of metabolites of meisoindigo in male and female rat kidney microsomes by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 22:3835–3845. 2008. View Article : Google Scholar

22 

Fura A: Role of pharmacologically active metabolites in drug discovery and development. Drug Discov Today. 11:133–142. 2006. View Article : Google Scholar

23 

Wee XK, Yeo WK, Zhang B, et al: Synthesis and evaluation of functionalized isoindigos as antiproliferative agents. Bioorg Med Chem. 17:7562–7571. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang M, Lin H, Lee YS and Ho PC: Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics. Int J Oncol 45: 1724-1734, 2014.
APA
Huang, M., Lin, H., Lee, Y.S., & Ho, P.C. (2014). Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics. International Journal of Oncology, 45, 1724-1734. https://doi.org/10.3892/ijo.2014.2548
MLA
Huang, M., Lin, H., Lee, Y. S., Ho, P. C."Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics". International Journal of Oncology 45.4 (2014): 1724-1734.
Chicago
Huang, M., Lin, H., Lee, Y. S., Ho, P. C."Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics". International Journal of Oncology 45, no. 4 (2014): 1724-1734. https://doi.org/10.3892/ijo.2014.2548
Copy and paste a formatted citation
x
Spandidos Publications style
Huang M, Lin H, Lee YS and Ho PC: Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics. Int J Oncol 45: 1724-1734, 2014.
APA
Huang, M., Lin, H., Lee, Y.S., & Ho, P.C. (2014). Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics. International Journal of Oncology, 45, 1724-1734. https://doi.org/10.3892/ijo.2014.2548
MLA
Huang, M., Lin, H., Lee, Y. S., Ho, P. C."Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics". International Journal of Oncology 45.4 (2014): 1724-1734.
Chicago
Huang, M., Lin, H., Lee, Y. S., Ho, P. C."Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics". International Journal of Oncology 45, no. 4 (2014): 1724-1734. https://doi.org/10.3892/ijo.2014.2548
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