Naphtho[1,2-b]furan-4,5-dione induces apoptosis of oral squamous cell carcinoma: involvement of EGF receptor/PI3K/Akt signaling pathway.

Abstract

Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exerts an anti-tumor effect. This study was performed to elucidate whether the epidermal growth factor (EGF) receptor and phosphatidylinositol-3-kinase (PI3K) signaling pathways are involved in NFD-induced apoptosis of oral squamous cell carcinoma (OSCC). Immunoblot showed that NFD suppressed the phosphorylation of EGF receptor and activation of PI3K/Akt, downstream molecules of EGF receptor signaling pathway, in Ca9-22 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 (NF kappaB), modulation of I kappa K beta and I kappaB alpha, up-regulation of Bad, and down-regulation of anti-apoptotic proteins including phospho-Bad, Bcl-X(L), myeloid cell leukemia-1(Mcl-1), and XIAP were found in NFD-treated cells. In addition, NFD treatment disrupted mitochondrial membrane potential (Delta Psi m), resulted in release of cytochrome c, and activation of both caspases-9 and caspase-3. Taken together, these results indicate that NFD induces apoptosis in Ca9-22 cells via inactivation of the EGF receptor-mediated survival pathway.

• Authors: Ching-Ming Chien, Kuei-Li Lin, Jung-Chen Su, Pei-Wen Chuang, Chih-Hua Tseng, Yeh-Long Chen, Long-Sen Chang, Shinne-Ren Lin
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 636 Issue 1-3 Pg. 52-8 (Jun 25 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20371243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Inhibitor of Apoptosis Proteins
• NF-kappa B
• Naphthoquinones
• naphtho(1,2-b)furan-4,5-dione
• Cytochromes c
• Phosphatidylinositol 3-Kinases
• ErbB Receptors
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytochromes c (metabolism)
• Enzyme Activation (drug effects)
• ErbB Receptors (metabolism)
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Mouth Neoplasms (metabolism, pathology)
• NF-kappa B (metabolism)
• Naphthoquinones (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)