Inhibition of GSH-dependent PGH 2 isomerase in mammary adenocarcinoma cells by allicin.

Abstract

We have reported tha allicin, a constituent of garlic oil, has no effect on the activities of platelet cyclooxygenase or thromboxane synthase, or vascular PGI 2 synthase. The effect of allicin on glutathione (GSH) dependent PGH 2 to PGE 2 isomerase is unknown. We therefore studied the effect of allicin on PGE 2 biosynthesis in a murine mammary adenocarcinoma cell line (No 4526). Intact or sonicated cells were incubated with either 14C-arachidonic acid (AA) or 14C-PHG 2, respectively. Following metabolism, products were extracted, separated by TLC and analyzed by radiochromatographic scan. PGE 2 was predominantly formed with minimal amounts of PGF 2α and PGD 2. Formation of 6-keto-PGF 1α or TXB 2 was not detected indicating the absence of TXA 2 and PGI 2 synthase activity. Indomethacin and ibuprofen inhibited the PGE 2 formation (p < 0.05). The enzymatic PGE 2 formation in sonicates was blocked by depletion of the cellular non-protein thiols by buthionine sulfoximine and was shown to be dependent on GSH. Allicin, over the range of 10–1000 μM, inhibited the formation of PGE 2 in cells exposed to 2.0 μM 14C-AA for 20 min. and in sonicated cells incubated with 20.0 μM 14C-PGH 2 for 2 min (p < 0.05). Allicin did not alter cyclooexygenase-mediated oxygen utilization in ram seminal vessicle microsomes, suggesting that allicin selectively inhibits the GSH-dependent PGH 2 to PGE 2 isomerase in this adenocarcinoma cell line.