Exposure of human breast cancer cells to the anti-inflammatory agent indomethacin alters choline phospholipid metabolites and Nm23 expression.
We previously observed that changes in choline phospholipids of two malignant human mammary epithelial cells (HMECs) following treatment with a high dose of the cyclooxygenase (COX) inhibitor, indomethacin, mimicked changes following transfection with a metastasis suppressor gene, nm23. The similarity between response to indomethacin and nm23 transfection led us to 1) expand our (1)H NMR spectroscopy study of indomethacin treatment by determining the response at two doses for two nonmalignant and three malignant HMECs, 2) investigate COX-1 and COX-2 levels in HMECs and their relationship with choline phosholipid metabolites, and 3) determine changes in Nm23 expression following treatment with indomethacin. All HMECs exhibited a significant change in choline phospholipids following treatment with 300 microM indomethacin. At the lower dose of 50 microM, only nonmalignant HMECs and the estrogen-dependent malignant cell line, MCF-7, responded. COX-1 levels were significantly higher in malignant HMECs than in nonmalignant HMECs. A significant increase in Nm23 expression following 300 microM indomethacin was detected in MCF-12A and MCF-7 cells but not in MDA-MB-231 and MDA-MB-435 cells. These results suggest that COX-1 expression and its inhibition play a role in the choline phospholipid metabolism of HMECs, and the effect of indomethacin on HMECs may be mediated, in part, through upregulation of nm23.
Department of Radiology, MR Oncology Section, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kshama
K
Natarajan
Noriko
N
Mori
Dmitri
D
Artemov
Zaver M
ZM
Bhujwalla
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005997:Glycerylphosphorylcholine / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D010767:Phosphorylcholine / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D010767:Phosphorylcholine; D005997:Glycerylphosphorylcholine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D002794:Choline; D007213:Indomethacin