Enhanced apoptosis-inducing effect of etoposide on leukemic cell lines M-07e and TF-1 by the proteasome inhibitor Z-LLL-CHO / 中国实验血液学杂志
Journal of Experimental Hematology
;
(6): 485-489, 2003.
Artigo
em Chinês
| WPRIM
| ID: wpr-278857
ABSTRACT
Recent researches indicate that ubiquitin-protea some pathway plays an important role in apoptosis regulation. Proteasome inhibitors induce apoptosis in many kinds of neoplastic cells, thus provide a great opportunity for exploring synergy of proteasome inhibitors and other apoptosis-inducing agents. In this study, the effect of the proteasome inhibitor Z-LLL-CHO combined with etoposide (VP16) on leukemic cell lines M-07e and TF-1 was investigated by MTT assay, trypan blue exclusion, flow cytometry and Western blot. The results showed that the combination of Z-LLL-CHO and VP16 was much more effective than either agents alone in promoting cytotoxicity in both cell lines evaluated. Accumulation of cells in S + G2/M phase of the cell cycle was observed in the cells treated with VP16 and Z-LLL-CHO alone, while apparent increase of sub-G0/G1 fraction was detected in cells treated with combination of the agents. The cleavage of Bcl-2 into a shortened 22 kD fragment was detected in M-07e cells exposed to either agents alone, and the fraction of 22 kD fragment was increased in the cells treated with combination of the agents. In conclusion, the combination of Z-LLL-CHO and VP16 enhanced their individual cytotoxic effect by inducing apoptosis, in which increase of S + G2/M fraction in cell cycle as well as the enhanced cleavage of Bcl-2 are the possible mechanism of the additive effect on leukemic cells by Z-LLL-CHO and VP16.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Oligopeptídeos
/
Patologia
/
Farmacologia
/
Cisteína Endopeptidases
/
Leucemia
/
Ciclo Celular
/
Apoptose
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Linhagem Celular Tumoral
/
Complexo de Endopeptidases do Proteassoma
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Experimental Hematology
Ano de publicação:
2003
Tipo de documento:
Artigo
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