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Inhibition of cyclooxygenase-2 expression and restoration of gap junction intercellular communication in H-ras-transformed rat liver epithelial cells by caffeic acid phenethyl ester

Cited 29 time in Web of Science Cited 30 time in Scopus
Authors
Lee, Ki Won; Chun, Kyung Soo; Lee, Jeong-Sang; Kang, Kyung Sun; Surh, Young-Joon; Lee, Hyong Joo
Issue Date
2004
Citation
Annals of the New York Academy of Sciences, Vol.1030, pp.501-507
Keywords
H-rascyclooxygenase-2gap junction intercellular communicationnuclear factor kappa Bcaffeic acid phenethyl esterrat liver epithelial cells
Abstract
One of the most frequent defects in human cancers is the uncontrolled activation of the ras signaling pathways. Increased expression of cyclooxygenase-2 (COX-2) and inhibition of gap junction intercellular communication (GJIC) have been frequently observed in several forms of human malignancies. The present study investigated the effects of caffeic acid phenethyl ester (CAPE), a chemopreventive phytochemical derived from honey propolis, on COX-2 expression and GJIC in Harvey-ras-transformed WB-F344 rat liver epithelial cells (H-ras WB cells). H-ras induced COX-2 expression in WB-F344 rat liver epithelial cells (WB cells). H-ras WB cells also exhibited complete inhibition of GJIC and predominant unphosphorylation of connexin 43 (Cx43), a major protein modulating GJIC. CAPE significantly inhibited the constitutive expression of COX-2 and restored the disrupted GJIC through the phosphorylation of Cx43 at a concentration of 12.5 mu M in H-ras WB cells. Although the molecular basis for the cancer chemopreventive activity of CAPE is not completely understood, several studies suggest that CAPE is a potent and specific inhibitor of the transcription factor nuclear factor B-K (NF-B-K) activation. We also found that CAPE significantly inhibited H-ras-induced NF-B-K DNA-binding activity without affecting the activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, which are major intracellular molecules involved in the Ras signaling pathways. In conclusion, CAPE may exert cancer chemopreventive effects through the inhibition of COX-2 expression and the restoration of disrupted GJIC induced by H-ras, possibly by targeting NF-B-K.
ISSN
0077-8923
URI
https://hdl.handle.net/10371/172843
DOI
https://doi.org/10.1196/annals.1329.062
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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