Effects of anthracycline derivatives on human leukemia K562 cell growth and differentiation

被引:28
作者
Czyz, M
Szulawska, A
Bednarek, AK
Düchler, M
机构
[1] Med Univ Lodz, Dept Mol Biol Canc, PL-92215 Lodz, Poland
[2] Med Univ Lodz, Dept Mol Cancerogenet, PL-92215 Lodz, Poland
[3] AKH Vienna, A-1090 Vienna, Austria
关键词
anticancer drugs; anthracycline derivatives; erythroid differentiation; growth arrest; K562; cells; differentiation therapy;
D O I
10.1016/j.bcp.2005.08.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
New derivatives of daunorubicin (DRB), doxorubicin (DOX), and epidoxorubicin (EDOX) with an amidine group bonded to C-3' of daunosamine moiety with either morpholine or hexamethyleneimine ring attached to the amidine group, are studied in this paper. We have shown that all of these newly synthesized anthracycline derivatives inhibit human leukemia K562 cell line proliferation but only some of them induce erythroid differentiation when used at subtoxic concentrations. Morpholine derivative of DOX has the greatest potential to inhibit proliferation and to induce differentiation in vitro. The correlation between these two cellular processes was also significant for other tested compounds. In cell cycle analysis, we have demonstrated that those anthracycline derivatives that exert the greatest cytostatic potential caused G(2)/M arrest, which in turn, might contribute to the development of a differentiating phenotype. The concentrations of the compounds used in the study are pharmacologically relevant. These new potent inducers of differentiation might be exploited as anticancer drugs for treatment of leukemia by differentiation therapy. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1431 / 1442
页数:12
相关论文
共 49 条
[1]   Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome c and activation of caspase-3 [J].
Amarante-Mendes, GP ;
Kim, CN ;
Liu, L ;
Huang, Y ;
Perkins, CL ;
Green, DR ;
Bhalla, K .
BLOOD, 1998, 91 (05) :1700-1705
[2]   Activation of erythroid-specific promoters during anthracycline-induced differentiation of K562 cells [J].
Aries, A ;
Trentesaux, C ;
Ottolenghi, S ;
Jardillier, JC ;
Jeannesson, P ;
Doubeikovski, A .
BLOOD, 1996, 87 (07) :2885-2890
[3]  
Belhacène N, 1998, FASEB J, V12, P531
[4]   Accumulation of γ-globin mRNA and induction of erythroid differentiation after treatment of human leukaemic K562 cells with tallimustine [J].
Bianchi, N ;
Chiarabelli, C ;
Borgatti, M ;
Mischiati, C ;
Fibach, E ;
Gambari, R .
BRITISH JOURNAL OF HAEMATOLOGY, 2001, 113 (04) :951-961
[5]   Induction of erythroid differentiation of human K562 cells by cisplatin analogs [J].
Bianchi, N ;
Ongaro, F ;
Chiarabelli, C ;
Gualandi, L ;
Mischiati, C ;
Bergamini, P ;
Gambari, R .
BIOCHEMICAL PHARMACOLOGY, 2000, 60 (01) :31-40
[6]   Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy [J].
Castedo, M ;
Perfettini, JL ;
Roumier, T ;
Valent, A ;
Raslova, H ;
Yakushijin, K ;
Horne, D ;
Feunteun, J ;
Lenoir, G ;
Medema, R ;
Vainchenker, W ;
Kroemer, G .
ONCOGENE, 2004, 23 (25) :4362-4370
[7]  
CHENG T, 1994, J BIOL CHEM, V269, P30848
[8]  
Constantinou AI, 1996, CANCER RES, V56, P4192
[9]  
Cortesi R, 1999, AM J HEMATOL, V62, P33, DOI 10.1002/(SICI)1096-8652(199909)62:1<33::AID-AJH6>3.0.CO
[10]  
2-M