GLUTAMINE SUPPRESSES PGE2 SYNTHESIS AND BREAST-CANCER GROWTH

Reduced natural killer (NK) activity found in tumor-bearing hosts has been associated with high levels of prostaglandin E2 (PGE2) produced b y monocytes in vitro. We have previously demonstrated a dependence of NK cell activity on glutamine (GLN) levels in vitro and in vivo. Furth er, glutathione (GSH) is antagonistic to PGE2 synthesis. We hypothesiz ed that GLN, through increased GSH production, leads to decreased PGE2 synthesis and upregulation of NK cytotoxic activity. To test this, we examined the effects of oral GLN on GSH and PGE2 concentrations, NK a ctivity and tumor growth in a rat breast cancer model. Starting on the day of MTF-7 tumor implantation 18 Fisher 344 rats were pair-fed chow and gavaged with 1 g/kg/day GLN (n = 9) or an isonitrogenous amount o f Freamine (FA) (n = 9). Seven weeks after tumor implantation rats wer e sacrificed. Tumors were measured, weighed, and processed for tumor m orphometrics. Spleens were removed, lymphocytes isolated and assayed f or NK activity. Blood GLN, GSH, and PGE2 concentrations were measured. Over the 7-week study period tumor growth was decreased by approximat ely 40% in the GLN-supplemented group. This decrease in growth was ass ociated with a 2.5 fold greater NK activity in the GLN-fed rats vs FA- fed rats. This correlated with a 25% rise in GSH concentration and a p roportional decrease in PGE2 synthesis. Decreased tumor volume in rats fed GLN was not associated with changes in morphometrics. Oral GLN su pplementation enhances NK activity resulting in decreased tumor growth . The enhanced NK activity seen with oral GLN supplementation in the t umor-bearing host is associated with GSH mediated suppression of PGE2 synthesis. (C) 1996 Academic Press, Inc.