Violacein and its beta-cyclodextrin complexes induce apoptosis and differentiation in HL60 cells.
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, IC(50) for the inclusion complexes (1:1 and 1:2 violacein:beta-CD molar ratios) and violacein alone were less than 1 microM. 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.
Melo
Patrícia S
PS
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, CP 6109, CEP 13083-970 Campinas, São Paulo, Brazil.
Justo
Giselle Z
GZ
de Azevedo
Mariângela B M
MB
Durán
Nelson
N
Haun
Marcela
M
D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2; D053178:Caspase 6; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003505:Cyclodextrins / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000737:chemistry / Q000633:toxicity*; D009580:Nitroblue Tetrazolium; D012394:Rosaniline Dyes; D014344:Trypanocidal Agents / Q000737:chemistry / Q000633:toxicity*; D047392:beta-Cyclodextrins
D004396:Coloring Agents; D003505:Cyclodextrins; C007722:Feulgen stain; D007202:Indicators and Reagents; D007211:Indoles; D012394:Rosaniline Dyes; D014344:Trypanocidal Agents; D047392:beta-Cyclodextrins; D009580:Nitroblue Tetrazolium; C505514:CASP6 protein, human; C506433:CASP9 protein, human; D053143:Caspase 2; D053178:Caspase 6; D053453:Caspase 9; D020169:Caspases; C031215:betadex; C063155:violacein