In vitro effects of eicosanoid synthesis inhibitors in the presence of linoleic acid on MDA-MB-231 human breast cancer

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 mu g/ml) of indomethacin (INDO) stimulated cell growth and thymidine incorporation, while a high concentration of IND O (30 mu g/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 PGE(2) partially reversed the inhibition of thymidine incorporation caused by INDO, whereas LTB(4) exerted a similar effect in the case of esculetin or NDGA. The reversibility of the piroxicam effect with PGE(2) is not convincing. Therefore, it is suggested that the growth of MDA-MB-231 cells in vitro is affected by both the lipoxygenase and cyclooxygenase products, probably the other eicosanoids rather than PGE(2) and LTB(4).