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  • Title: Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation.
    Author: Su JC, Lin KL, Chien CM, Lu CM, Chen YL, Chang LS, Lin SR.
    Journal: Life Sci; 2009 Sep 23; 85(13-14):505-16. PubMed ID: 19699753.
    Abstract:
    AIMS: This study was performed to elucidate whether mitogen-activated protein kinases (MAPKs) are involved in the modulation of apoptosis and cell-cycle arrest by N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (IQDMA), in human lung adenocarcinoma A549 cells. MAIN METHODS: The effect of IQDMA on cell-cycle arrest and apoptosis was measured by flow cytometry, and phosphorylation levels of mitogen-activated protein kinases (MAPKs) and its regulatory molecules were studied by immunoblots. KEY FINDINGS: IQDMA-induced G(2)/M arrest was associated with a marked decrease in the protein expressions of cyclin A, cyclin B, and cyclin-dependent kinase (Cdk)1. IQDMA-induced apoptosis was accompanied with up-regulation of the protein expression of Bax and down-regulation of the protein levels of Bcl-2, Mcl-1, X-linked inhibitor of apoptosis (XIAP), and survivin, resulting in cytochrome c release and sequential activation of caspase-9 and caspase-3. IQDMA activated c-Jun N-terminal kinase (JNK), p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) on A549 cells in a time-dependent manner. Unlike the ERK inhibitor (PD98059), inhibitors of JNK (SP600125) and p38 MAPK (SB203580) suppressed IQDMA-induced apoptosis and G(2)/M phase arrest in A549 cells. Both SP600125 and SB203580 attenuated the activation of Bax and cytochrome c release, and reversed down-regulation of Bcl-2, XIAP, survivin, cyclin A, cyclin B, and Cdk1 in IQDMA-treated cells. SIGNIFICANCE: These findings indicate that JNK/p38 MAPK pathways play an important role in IQDMA-induced G(2)/M arrest and apoptosis of A549 cells.
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