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 inhibit ors in the presence of linoleic acid (LA), as well as the direct effec ts of prostaglandin E (PGE) and leukotriene B (LTB) on a human breast cancer cell line (MDA-MB-231) in vitro. Piroxicam, esculetin, and nord ihydroguaiaretic acid (NDGA) suppressed cell growth and thymidine inco rporation. However, a low concentration (1 mu g/ml) of indomethacin (I NDO) 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 co rrelated with the PGE and/or LTB concentrations when the cells were tr eated with these cyclooxygenase or lipoxygenase inhibitors. On the oth er hand, exogenous PGE(2) partially reversed the inhibition of thymidi ne incorporation caused by INDO, whereas LTB(4) exerted a similar effe ct in the case of esculetin or NDGA. The reversibility of the piroxica m effect with PGE(2) is not convincing. Therefore, it is suggested tha t the growth of MDA-MB-231 cells in vitro is affected by both the lipo xygenase and cyclooxygenase products, probably the other eicosanoids r ather than PGE(2) and LTB(4).