TY - JOUR
T1 - Glutamine suppresses PGE2 synthesis and breast cancer growth
AU - Klimberg, V. Suzanne
AU - Kornbluth, Jacki
AU - Cao, Yihong
AU - Dang, A.
AU - Blossom, Sarah
AU - Schaeffer, Robert F.
N1 - Funding Information:
1This work was supported by a grant from the American Cancer Society.
PY - 1996/6
Y1 - 1996/6
N2 - 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 INK 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.
AB - 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 INK 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.
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U2 - 10.1006/jsre.1996.0263
DO - 10.1006/jsre.1996.0263
M3 - Article
C2 - 8661213
AN - SCOPUS:0029887479
SN - 0022-4804
VL - 63
SP - 293
EP - 297
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -