In vitro effects of eicosanoid synthesis inhibitors in the presence of linoleic acid on MDA-MB-231 human breast cancer cells
We investigated the effects of cyclooxygenase and lipoxygenase inhibitors in the presence of linoleic acid (LA), as well as the direct effects of prostaglandin E (PGE) and leukotriene B (LTB) on a human breast cancer cell line (MDA-MB-231)in vitro. Piroxicam, esculetin, and nordihydroguaiaretic acid (NDGA) suppressed cell growth and thymidine incorporation. However, a low concentration (1 µg/ml) of indomethacin (INDO) stimulated cell growth and thymidine incorporation, while a high concentration of INDO (30 µg/ml) inhibited both. Esculetin and NDGA reduced the secretion of LTB, whereas piroxicam reduced the secretion of PGE. INDO reduced the secretion of PGE, but a low concentration of INDO increased the secretion of LTB. Consequently, cell growth was correlated with the PGE and/or LTB concentrations when the cells were treated with these cyclooxygenase or lipoxygenase inhibitors. On the other hand, exogenous PGE2 partially reversed the inhibition of thymidine incorporation caused by INDO, whereas LTB4 exerted a similar effect in the case of esculetin or NDGA. The reversibility of the piroxicam effect with PGE2 is not convincing. Therefore, it is suggested that the growth of MDA-MB-231 cellsin vitro is affected by both the lipoxygenase and cyclooxygenase products, probably the other eicosanoids rather than PGE2 and LTB4.
Key wordsbreast cancer esculetin indomethacin linoleic acid NDGA piroxicam
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- 5.Carter CA, Milholland RJ, Shea W, Ip MM: Effect of the prostaglandin synthetase inhibitor indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat. Cancer Res 38: 3559–3562, 1983Google Scholar
- 16.Noguchi M, Taniya T, Koyasaki N, Kumaki T, Miyazaki I, Mizukami Y: Effects of the prostaglandin synthetase inhibitor indomethacin on tumorigenesis, tumor proliferation, cell kinetics, and receptor contents of 7,12-dimethylbenz(a) anthracene-induced mammary carcinoma in Spague-Dawley rats fed a high- or low-fat diet. Cancer Res 51: 2683–2689, 1991PubMedGoogle Scholar
- 34.Parker CW: Leukotrienes and prostaglandins in the immune system. In: Zor U, Naor Z, Kohen F (eds) Advances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 16. Raven Press, New York, 1986, pp 113–134Google Scholar
- 43.Hobbs DC: Pharmacokinetics of piroxicam in man. Eur J Rheum Inflamm 6: 46–55, 1983Google Scholar
- 47.Maloff BL, Fefer D, Cooke GM, Ackerman NR: Inhibition of LTB4 binding to human neutrophils by nordihydroguaiaretic acid. Agents Action 21: 358–360, 1987Google Scholar