Violacein and its β-cyclodextrin complexes induce apoptosis and differentiation in HL60 cells

被引:72
作者
Melo, PS
Justo, GZ
de Azevedo, MBM
Durán, N
Haun, M
机构
[1] Univ Estadual Campinas, Inst Biol, Dept Bioquim, BR-13083970 Campinas, SP, Brazil
[2] Univ Estadual Campinas, Fac Ciencias Med, Dept Farmacol, BR-13083970 Campinas, SP, Brazil
[3] Univ Estadual Campinas, Inst Quim, Biol Chem Lab, BR-13083970 Campinas, SP, Brazil
[4] Univ Mogi das Cruzes, BR-08790911 Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
violacein; HL60; cells; beta-cyclodextrin; inclusion complex; differentiation; apoptosis;
D O I
10.1016/S0300-483X(02)00751-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Violacein, a pigment isolated from Chromobacterium violaceum, has been reported to have multiple biological activities including in vitro antitumor effects. Certain anticancer agents are known to induce apoptosis in human tumor cell lines. In this work, our aim was to investigate the effectiveness of violacein/beta-cyclodextrin (beta-CD)-containing systems to produce lethal effects in the human promyelocytic leukemia cell line HL60. Using the MTT tetrazolium reduction test, IC50 for the inclusion complexes (1:1 and 1:2 violacein:beta-CD molar ratios) and violacein alone were less than 1 muM. Violacein and violacein/beta-CD complexes were able to induce NBT reduction. Moreover, by using the Feulgen reaction, all the compounds were found to trigger apoptosis in HL60 cells, inducing around 35% of DNA fragmentation, as analyzed through the diphenylamine assay. In addition, caspases seem to play an important role in the activation of the executioner phase of apoptosis induced by violacein and its derivatives. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:217 / 225
页数:9
相关论文
共 27 条
[1]   Caspases: the executioners of apoptosis [J].
Cohen, GM .
BIOCHEMICAL JOURNAL, 1997, 326 :1-16
[2]   Cytotoxicity and cell cycle effects of the plant alkaloids cryptolepine and neocryptolepine: relation to drug-induced apoptosis [J].
Dassonneville, L ;
Lansiaux, A ;
Wattelet, A ;
Wattez, N ;
Mahieu, C ;
Van Miert, S ;
Pieters, L ;
Bailly, C .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2000, 409 (01) :9-18
[3]   Violacein/β-cyclodextrin inclusion complex formation studied by measurements of diffusion coefficient and circular dichroism [J].
De Azevedo, MBM ;
Alderete, JB ;
Lino, ACS ;
Loh, W ;
Faljoni-Alario, A ;
Durán, N .
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, 2000, 37 (1-4) :67-74
[4]   Biological activities of violacein, a new antitumoral indole derivative, in an inclusion complex with β-cyclodextrin [J].
De Azevedo, MBM ;
Alderete, J ;
Rodriguez, JA ;
Souza, AO ;
Rettori, D ;
Torsoni, MA ;
Faljoni-Alario, A ;
Haun, M ;
Durán, N .
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, 2000, 37 (1-4) :93-101
[5]   Chromobacterium violaceum:: A review of pharmacological and industiral perspectives [J].
Durán, N ;
Menck, CFM .
CRITICAL REVIEWS IN MICROBIOLOGY, 2001, 27 (03) :201-222
[6]   Apoptosis [J].
Israels, LG ;
Israels, ED .
STEM CELLS, 1999, 17 (05) :306-313
[7]   Induction of differentiation and apoptosis by dithizone in human myeloid leukemia cell lines [J].
Kohroki, J ;
Norio, MA ;
Tanaka, T ;
Itoh, N ;
Inada, A ;
Tanaka, K .
LEUKEMIA RESEARCH, 1998, 22 (05) :405-412
[8]   EVALUATION OF THE CYTOTOXICITY OF CYCLODEXTRINS AND HYDROXYPROPYLATED DERIVATIVES [J].
LEROYLECHAT, F ;
WOUESSIDJEWE, D ;
ANDREUX, JP ;
PUISIEUX, F ;
DUCHENE, D .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1994, 101 (1-2) :97-103
[9]  
Melo PD, 2000, IN VITRO CELL DEV-AN, V36, P539, DOI 10.1290/1071-2690(2000)036<0539:VCAIOA>2.0.CO
[10]  
2