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.
journal_name
Life Scijournal_title
Life sciencesauthors
Su JC,Lin KL,Chien CM,Tseng CH,Chen YL,Chang LS,Lin SRdoi
10.1016/j.lfs.2009.12.006subject
Has Abstractpub_date
2010-01-30 00:00:00pages
207-13issue
5-6eissn
0024-3205issn
1879-0631pii
S0024-3205(09)00493-7journal_volume
86pub_type
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