Authors
Klimberg VS. Kornbluth J. Cao Y. Dang A. Blossom S. Schaeffer RF.
Institution
University of Arkansas for Medical Siences, Department of Surgery, Little
Rock 72205, USA.
Title
Glutamine suppresses PGE2 synthesis and breast cancer
growth.
Source
Journal of Surgical Research. 63(1):293-7, 1996 Jun.
Abstract
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.