Non-steroidal anti-inflammatory drugs and tumor progression: inhibition of fibroblast hyaluronic acid production by indomethacin and mefenamic acid.
The antitumor effects of non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in a variety of both clinical and experimental settings, although the mechanisms responsible remain unclear. In the present study, we show that the NSAIDs indomethacin and mefenamic acid inhibit the calf serum-stimulated production of hyaluronic acid (HA) in murine Swiss 3T3 fibroblasts, at concentrations where DNA synthesis is unaffected. HA is an extracellular matrix glycosaminoglycan associated with cell migration and tumor invasion. Our data suggest that one mechanism whereby NSAIDs inhibit tumor progression may be to inhibit the synthesis of HA by host fibroblasts, and that the eicosenoid pathway may represent an important control point in the growth-factor-mediated production of HA in fibroblasts. Thus the use of an agent which inhibits HA synthesis may be a novel approach to alter the invasive and metastatic properties of tumor cells in a non-cytotoxic fashion.
August
E M
EM
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Nguyen
T
T
Malinowski
N M
NM
Cysyk
R L
RL
D016475:3T3 Cells; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology*; D008528:Mefenamic Acid / Q000494:pharmacology*; D051379:Mice
D008528:Mefenamic Acid; D006820:Hyaluronic Acid; D004247:DNA; D007213:Indomethacin