Exposure of Human Breast Cancer Cells to the Anti-inflammatory Agent Indomethacin Alters Choline Phospholipid Metabolites and Nm23 Expression

Abstract

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 nm23transfection led us to 1) expand our 1H 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, 3) determine changes in Nm23 expression following treatment with indomethacin. All HMECs exhibited a significant change in choline phospholipids following treatment with 300 µM indomethacin. At the lower dose of 50 pM, only nonmalignant HMECs and the estrogen-dependent malignant cell line, MCF-7, responded. COX-1 levelswere significantly higher in malignant HMECs than in nonmalignant HMECs. A significant increase in Nm23 expression following 300 pM indomethacin was detected in MCF12A and MCF-7 cells but not in MDA-MB-231 and MDAMB-435 cells. These results suggest that COX-1 expression and its inhibition play a role in the choline phospholipid metabolism of HMECs, the effect of indomethacin on HMECs may be mediated, in part, through upregulation of nm23.

Keywords

• anti-inflammatory agent
• breast cancer cells
• Nm23 expression
• NMR spectroscopy
• choline phospholipid metabolites