Phospholipid profiles of invasive human breast cancer cells are altered towards a less invasive phospholipid profile by the anti-inflammatory agent indomethacin

K. Natarajan, N. Mori, D. Artemov, E. O. Aboagye, V. P. Chacko, Z. M. Bhujwalla

Research output: Contribution to journalArticle

Abstract

We recently demonstrated that human mammary epithelial cells exhibit alterations in choline phospholipids with progression to the malignant phenotype (3). Further evidence of the role of the choline phospholipid compounds in breast cancer progression also comes from our studies of the metastatic human breast cancer line MDA-MB-435 following transection with the nonmetastatic gene nm23 (4). Several studies have shown that the nonsteroidal anti-inflammatory agent indomethacin can inhibit the invasive and metastatic behavior of human breast cancer cells. We therefore studied the effects of indomethacin on the phospholipid compounds of two malignant human breast cancer cell lines and an immortalized human mammary epithelial cell line. Proton spectra obtained from cell extracts of malignant MDA-MB-435 and 231 cells showed a significant increase of GPC following incubation with 300 μM indomethacin for 3 h. Indomethacin, a nonspecific cyclooxygenase (COX) inhibitor, altered the phospholipid profile of malignant breast cancer cells toward a less malignant phospholipid phenotype. Characterization of COX-1 and COX-2 expressions revealed that the pattern of COX-1 but not COX-2 expression for these cell lines matched the phospholipid pattern. Basal PGE2 expression, as well as expression following stimulation with TPA, appeared to be coupled to COX-2 rather than COX-1 expression. Following treatment with indomethacin, intracellular PGE2 levels decreased for MDA-MB-231 cells only. These results suggest that the altered phospholipid profile of highly malignant breast cancer cells may partly be related to alterations of the COX-1/COX-2 pathway. These results also provide direct evidence that the phospholipid peaks in NMR spectra of breast cancer cells can be modulated by a COX inhibitor and indicate the utility of NMR in understanding the role of anti-inflammatory agents in cancer treatment.

Original languageEnglish (US)
Pages (from-to)271-284
Number of pages14
JournalAdvances in Enzyme Regulation
Volume40
Issue number1
DOIs
StatePublished - Jun 1 2000

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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