Reduced natural killer (NK) activity found in
tumor-bearing hosts has been associated with high levels of
prostaglandin E2 (
PGE2) produced by monocytes in vitro. We have previously demonstrated a dependence of NK cell activity on
glutamine (GLN) levels in vitro and in vivo. Further,
glutathione (GSH) is antagonistic to
PGE2 synthesis. We hypothesized 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 activity 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 of
Freamine (FA) (n = 9). Seven weeks after
tumor implantation rats were sacrificed.
Tumors were measured, weighed, and processed for
tumor morphometrics. Spleens were removed, lymphocytes isolated and assayed for NK activity. Blood GLN, GSH, and
PGE2 concentrations were measured. Over the 7-week study period
tumor growth was decreased by approximately 40% in the GLN-supplemented group. This decrease in growth was associated 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 proportional decrease in
PGE2 synthesis. Decreased
tumor volume in rats fed GLN was not associated with changes in morphometrics. Oral GLN supplementation enhances NK activity resulting in decreased
tumor growth. The enhanced NK activity seen with oral GLN supplementation in the
tumor-bearing host is associated with GSH mediated suppression of
PGE2 synthesis.