Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line.
Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the anti-inflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDA-MB-435 in Dulbecco's Modified Eagles (DME)-based or Roswell Park Memorial Institute (RPMI)-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG) concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenase-independent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.
Ackerstaff
Ellen
E
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gimi
Barjor
B
Artemov
Dmitri
D
Bhujwalla
Zaver M
ZM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009361:Neoplasm Invasiveness; D010713:Phosphatidylcholines / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010713:Phosphatidylcholines; D014280:Triglycerides; D011451:Prostaglandin-Endoperoxide Synthases; D020778:Matrix Metalloproteinase 2; D007213:Indomethacin