Tags

Type your tag names separated by a space and hit enter

Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells.
Life Sci. 2010 Jan 30; 86(5-6):207-13.LS

Abstract

AIMS

Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits an anti-carcinogenic effect. This study was performed to elucidate whether EGFR and PI3K signaling pathways are involved in NFD-induced apoptosis of human lung adenocarcinoma A549 cells.

MAIN METHODS

The effect of NFD on cell viability and apoptosis was measured by the MTT assay and flow cytometry. The phosphorylation levels of EGFR and its regulatory molecules by NFD treatment were studied by immunoblots.

KEY FINDINGS

Immunoblot showed that NFD inhibited EGFR phosphorylation and the activation of PI3K/Akt, downstream molecules of EGFR pathway, in A549 cells. The levels of downstream targets of Akt, including phospho-glycogen synthase kinase-3beta (p-GSK-3beta), GSK-3beta, forkhead transcription factor (FKHR), and cyclin D1, were also reduced after NFD treatment. Moreover, inactivation of nuclear factor-kappaB (NFkappaB), modulation of IkappaKalpha/beta and IkappaBalpha, up-regulation of Bad and Bax, and down-regulation of anti-apoptotic proteins including phospho-Bad, Bcl-2, survivin, and XIAP were also found in NFD-treated cells. In addition, NFD treatment disrupted mitochondrial membrane potential (DeltaPsim) and resulted in release of mitochondrial cytochrome c and activation of both caspases-9 and caspase-3.

SIGNIFICANCE

These findings indicate that EGFR and PI3K/Akt signaling pathways play important roles in NFD-induced 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

20036260

Citation

Su, Jung-Chen, et al. "Naphtho[1,2-b]furan-4,5-dione Inactivates EGFR and PI3K/Akt Signaling Pathways in Human Lung Adenocarcinoma A549 Cells." Life Sciences, vol. 86, no. 5-6, 2010, pp. 207-13.
Su JC, Lin KL, Chien CM, et al. Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells. Life Sci. 2010;86(5-6):207-13.
Su, J. C., Lin, K. L., Chien, C. M., Tseng, C. H., Chen, Y. L., Chang, L. S., & Lin, S. R. (2010). Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells. Life Sciences, 86(5-6), 207-13. https://doi.org/10.1016/j.lfs.2009.12.006
Su JC, et al. Naphtho[1,2-b]furan-4,5-dione Inactivates EGFR and PI3K/Akt Signaling Pathways in Human Lung Adenocarcinoma A549 Cells. Life Sci. 2010 Jan 30;86(5-6):207-13. PubMed PMID: 20036260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells. AU - Su,Jung-Chen, AU - Lin,Kuei-Li, AU - Chien,Ching-Ming, AU - Tseng,Chih-Hua, AU - Chen,Yeh-Long, AU - Chang,Long-Sen, AU - Lin,Shinne-Ren, Y1 - 2009/12/28/ PY - 2009/11/03/received PY - 2009/12/04/accepted PY - 2009/12/29/entrez PY - 2009/12/29/pubmed PY - 2010/2/23/medline SP - 207 EP - 13 JF - Life sciences JO - Life Sci. VL - 86 IS - 5-6 N2 - AIMS: Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits an anti-carcinogenic effect. This study was performed to elucidate whether EGFR and PI3K signaling pathways are involved in NFD-induced apoptosis of human lung adenocarcinoma A549 cells. MAIN METHODS: The effect of NFD on cell viability and apoptosis was measured by the MTT assay and flow cytometry. The phosphorylation levels of EGFR and its regulatory molecules by NFD treatment were studied by immunoblots. KEY FINDINGS: Immunoblot showed that NFD inhibited EGFR phosphorylation and the activation of PI3K/Akt, downstream molecules of EGFR pathway, in A549 cells. The levels of downstream targets of Akt, including phospho-glycogen synthase kinase-3beta (p-GSK-3beta), GSK-3beta, forkhead transcription factor (FKHR), and cyclin D1, were also reduced after NFD treatment. Moreover, inactivation of nuclear factor-kappaB (NFkappaB), modulation of IkappaKalpha/beta and IkappaBalpha, up-regulation of Bad and Bax, and down-regulation of anti-apoptotic proteins including phospho-Bad, Bcl-2, survivin, and XIAP were also found in NFD-treated cells. In addition, NFD treatment disrupted mitochondrial membrane potential (DeltaPsim) and resulted in release of mitochondrial cytochrome c and activation of both caspases-9 and caspase-3. SIGNIFICANCE: These findings indicate that EGFR and PI3K/Akt signaling pathways play important roles in NFD-induced apoptosis of A549 cells. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/20036260/Naphtho[12_b]furan_45_dione_inactivates_EGFR_and_PI3K/Akt_signaling_pathways_in_human_lung_adenocarcinoma_A549_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(09)00493-7 DB - PRIME DP - Unbound Medicine ER -