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ET-18-O-CH3-induced apoptosis is causally linked to COX-2 upregulation in H-ras transformed human breast epithelial cells

Cited 16 time in Web of Science Cited 16 time in Scopus
Authors
Na, Hye-Kyung; Inoue, Hiroyasu; Surh, Young-Joon
Issue Date
2005-11
Citation
FEBS Letters, Vol.579 No.27, pp.6279-6287
Keywords
cyclooxygenase-2apoptosisET-18-O-CH315-deoxy-triangle(12,14)-prostaglandin J(2)human breast epithelial cells transformed with H-ras (MCF10A-ras)
Abstract
Abnormally elevated expression of cyclooxygenase-2 (COX-2) has been frequently observed in transformed or malignant cells, and certain non-steroidal anti-inflammatory drugs with COX-2 inhibitory activity exert anti-neoplastic or chemopreventive effects. Contrary to this notion, we have found that a novel alkylphospholipid type antitumor agent ET-18-O-CH3 (1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine) induces COX-2 expression in H-ras transformed human breast epithelial cells (MCF10A-ras) while it causes apoptosis at the same concentration range. The addition of a selective COX-2 inhibitor SC-58635 and COX-2 gene knock down with the siRNA blocked ET-18-O-CH3-induced apoptosis, suggesting that COX-2 induction by this drug is causally linked to its apoptosis inducing activity. ET-18-O-CH3 enhanced the transcriptional activities of cyclic AMP response element which is a key regulator of COX-2 expression. 15-Deoxy-Delta-(12,14) prostaglandin J(2) is, an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma), has been known to possess proapoptotic potential in diverse cell types. ET-18-O-CH3 treatment resulted in elevated release of 15d-PGJ(2) and DNA binding and transcriptional activity of PPAR gamma. Based on these findings, it is likely that ET-18-O-CH3 induces COX-2 expression and production of 15d-PGJ2 which may mediate the ET-18-O-CH3-induced apoptosis in MCF10A-ras cells. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
ISSN
0014-5793
URI
https://hdl.handle.net/10371/172743
DOI
https://doi.org/10.1016/j.febslet.2005.09.094
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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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