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Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation.
Life Sci. 2009 Sep 23; 85(13-14):505-16.LS

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.

Authors+Show Affiliations

Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19699753

Citation

Su, Jung-Chen, et al. "Novel Indoloquinoline Derivative, IQDMA, Induces G(2)/M Phase Arrest and Apoptosis in A549 Cells Through JNK/p38 MAPK Signaling Activation." Life Sciences, vol. 85, no. 13-14, 2009, pp. 505-16.
Su JC, Lin KL, Chien CM, et al. Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation. Life Sci. 2009;85(13-14):505-16.
Su, J. C., Lin, K. L., Chien, C. M., Lu, C. M., Chen, Y. L., Chang, L. S., & Lin, S. R. (2009). Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation. Life Sciences, 85(13-14), 505-16. https://doi.org/10.1016/j.lfs.2009.08.006
Su JC, et al. Novel Indoloquinoline Derivative, IQDMA, Induces G(2)/M Phase Arrest and Apoptosis in A549 Cells Through JNK/p38 MAPK Signaling Activation. Life Sci. 2009 Sep 23;85(13-14):505-16. PubMed PMID: 19699753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel indoloquinoline derivative, IQDMA, induces G(2)/M phase arrest and apoptosis in A549 cells through JNK/p38 MAPK signaling activation. AU - Su,Jung-Chen, AU - Lin,Kuei-Li, AU - Chien,Ching-Ming, AU - Lu,Chih-Ming, AU - Chen,Yeh-Long, AU - Chang,Long-Sen, AU - Lin,Shinne-Ren, Y1 - 2009/08/21/ PY - 2009/04/14/received PY - 2009/07/27/revised PY - 2009/08/05/accepted PY - 2009/8/25/entrez PY - 2009/8/25/pubmed PY - 2009/10/14/medline SP - 505 EP - 16 JF - Life sciences JO - Life Sci VL - 85 IS - 13-14 N2 - 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/19699753/Novel_indoloquinoline_derivative_IQDMA_induces_G_2_/M_phase_arrest_and_apoptosis_in_A549_cells_through_JNK/p38_MAPK_signaling_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(09)00333-6 DB - PRIME DP - Unbound Medicine ER -