Involvement of c-Jun N-terminal kinase in G2/M arrest and FasL-mediated apoptosis induced by a novel indoloquinoline derivative, IQDMA, in K562 cells.
Leuk Res
; 31(10): 1413-20, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17397922
ABSTRACT
N'-(11H-Indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (IQDMA), an indoloquinoline derivative, synthesized in our laboratory, has been demonstrated to be an effective anti-tumor agent in human leukemia cells. Treatment of K562 cells with IQDMA resulted in G2/M phase cell cycle arrest, presumably involving the concomitant up-regulation of p21 and apoptosis through up-regulation of FasL and sequential activation of caspase-8 and caspase-3. In contrast to the lack of appreciable effect on the phosphorylation of ERK and p38 MAPK, activation of JNK was noted when K562 cells were exposed to IQDMA. Moreover, IQDMA-mediated G2/M phase arrest and apoptosis were reversed after treatment with the JNK-specific inhibitors, SP600125 and JNK inhibitor 1. Further investigation showed that SP600125 reduced the activation of FasL, caspase-3, caspase-8, and led to a marked decline of p21. Taken together, our data show that JNK plays an important role in IQDMA-mediated G2/M arrest and apoptosis of K562 cancer cells.
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Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Ciclo Celular
/
Apoptose
/
Proteínas Quinases JNK Ativadas por Mitógeno
/
Indóis
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article