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Naphtho[1,2-b]furan-4,5-dione induces apoptosis of oral squamous cell carcinoma: involvement of EGF receptor/PI3K/Akt signaling pathway.
Eur J Pharmacol. 2010 Jun 25; 636(1-3):52-8.EJ

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+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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20371243

Citation

Chien, Ching-Ming, et al. "Naphtho[1,2-b]furan-4,5-dione Induces Apoptosis of Oral Squamous Cell Carcinoma: Involvement of EGF receptor/PI3K/Akt Signaling Pathway." European Journal of Pharmacology, vol. 636, no. 1-3, 2010, pp. 52-8.
Chien CM, Lin KL, Su JC, et al. Naphtho[1,2-b]furan-4,5-dione induces apoptosis of oral squamous cell carcinoma: involvement of EGF receptor/PI3K/Akt signaling pathway. Eur J Pharmacol. 2010;636(1-3):52-8.
Chien, C. M., Lin, K. L., Su, J. C., Chuang, P. W., Tseng, C. H., Chen, Y. L., Chang, L. S., & Lin, S. R. (2010). Naphtho[1,2-b]furan-4,5-dione induces apoptosis of oral squamous cell carcinoma: involvement of EGF receptor/PI3K/Akt signaling pathway. European Journal of Pharmacology, 636(1-3), 52-8. https://doi.org/10.1016/j.ejphar.2010.03.030
Chien CM, et al. Naphtho[1,2-b]furan-4,5-dione Induces Apoptosis of Oral Squamous Cell Carcinoma: Involvement of EGF receptor/PI3K/Akt Signaling Pathway. Eur J Pharmacol. 2010 Jun 25;636(1-3):52-8. PubMed PMID: 20371243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Naphtho[1,2-b]furan-4,5-dione induces apoptosis of oral squamous cell carcinoma: involvement of EGF receptor/PI3K/Akt signaling pathway. AU - Chien,Ching-Ming, AU - Lin,Kuei-Li, AU - Su,Jung-Chen, AU - Chuang,Pei-Wen, AU - Tseng,Chih-Hua, AU - Chen,Yeh-Long, AU - Chang,Long-Sen, AU - Lin,Shinne-Ren, Y1 - 2010/04/02/ PY - 2009/09/22/received PY - 2010/02/22/revised PY - 2010/03/14/accepted PY - 2010/4/8/entrez PY - 2010/4/8/pubmed PY - 2010/8/10/medline SP - 52 EP - 8 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 636 IS - 1-3 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20371243/Naphtho[12_b]furan_45_dione_induces_apoptosis_of_oral_squamous_cell_carcinoma:_involvement_of_EGF_receptor/PI3K/Akt_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(10)00227-X DB - PRIME DP - Unbound Medicine ER -