Glutamine Suppresses PGE2 Synthesis and Breast Cancer Growth

Klimberg, V. Suzanne; Kornbluth, Jacki; Cao, Yanjia; Dang, Alexander; Blossom, Sarah J.; Schaeffer, R.

doi:10.1006/jsre.1996.0263

Cited by 48 publications

(40 citation statements)

References 4 publications

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“…Further studies with DMBAinduced breast cancer have shown that GLN supplementation reduced tumor growth and reversed the depressed GSH levels in normal tissue [22,23]. This was associated with up-regulation of the decreased NK cell activity and decreased levels of IGF-1 and TGF-b in the circulation [24][25][26]. In the present study we examined the effect of dietary GLN on GSH content and activation of apoptosis in DMBA-induced mammary tumors of SpragueDawley rats.…”

Section: Introductionmentioning

confidence: 89%

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

Тодорова

Harms

Kaufmann

et al. 2004

Breast Cancer Res Treat

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Glutamine (GLN) is a non-essential amino acid that is present in nearly every biochemical pathway and is the major intraorgan nitrogen carrier. GLN via glutamate, is one of the precursors for the synthesis of glutathione (GSH), the major endogenous antioxidant in mammalian cells, which protects them from oxidative injury and cell death. Cancer cells have higher GSH levels than the surrounding normal cells, which attributes to a higher rate of cell proliferation and resistance to chemotherapy. Therefore, selective tumor depletion of GSH presents a promising strategy in cancer treatment. Experimental studies have associated decreased GSH levels with inhibition of proliferation and stimulation of apoptosis. Previous results of our laboratory have provided evidence that dietary GLN diminished tumor development in implantable as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer and elevated GSH in the host tissues. In this study we examined the effects of GLN on GSH levels in DMBA-induced mammary tumors and correlated the results with protein and mRNA expression of apoptosis-related proteins Bcl-2, Bax and caspase-3 in tumor cells. The results have shown that GLN supplementation caused a significant decrease in the tumor GSH levels and the ratio GSH/oxidized GSH (GSSG), accompanied by up-regulation of Bax and caspase-3, and down-regulation of Bcl-2. These findings suggest that dietary GLN supplementation suppresses mammary carcinogenesis by activation of apoptosis in tumor cells and this probably is a result of GSH down-regulation.

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Section: Introductionmentioning

confidence: 89%

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

Тодорова

Harms

Kaufmann

et al. 2004

Breast Cancer Res Treat

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“…There is a small but intriguing literature demonstrating that increased oral intakes of glutamine, administered at 1 g/kg/d in most studies, markedly slow the growth (by about 40%) of a range of transplanted tumors-a sarcoma, the MTF-7 breast cancer, and Morris hepatoma 7777-in rats while also suppressing the induction of breast cancer with DMBA; the effect on DMBA carcinogenesis was exerted at the promotional stage. [94][95][96][97] These benefits were associated with a marked increase in NK cytotoxicity; it was suspected that this was at least partially responsible for the observed tumor retardation. NK cells, like other lymphocytes, make prominent use of glutamine as an energy substrate and precursor for nucleotides, but whether this explains the observed marked impact on NK cytotoxicity is unclear.…”

Section: Boosting Immune Defenses: Focus On Natural Killer Cellsmentioning

confidence: 99%

Toward a Core Nutraceutical Program for Cancer Management

McCarty

Block

2006

Integr Cancer Ther

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As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroom β-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, β-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and β-hydroxy-β-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-κB activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

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“…In vivo evidence has documented increased NK cell activity with supplemental GLN. 5 In a previous study by Klimberg et al, 13 researchers showed that reduced NK activity observed in tumor-bearing hosts was associated with high levels of prostaglandin produced by monocytes in vitro. Previously, the researchers demonstrated a dependence of NK cell activity on GLN levels in vitro and in vivo.…”

Section: Immune System Effects Of Glnmentioning

confidence: 96%

“…They also found that neither GLN nor GSH levels in the tumors were increased by GLN supplementation; 11 other researchers have observed similar results. 4,5,7,13 According to one dose-finding review article, no toxic side effects were found in any studies using oral or parenteral GLN supplementation, with ranges from 0.2 to 0.65 g of GLN/kg/d in pediatric oncology patients, with plasma GLN and ammonia comparing favorably in safety and metabolic effects. 34 Dosage ranges may vary depending on the status of the individual patients' liver enzymes because GLN can raise the levels of liver transaminases (AST and ALT), as seen anecdotally in clinical practice.…”

Section: Toxicitymentioning

confidence: 99%

L-Glutamine Use in the Treatment and Prevention of Mucositis and Cachexia: A Naturopathic Perspective

Noé

2009

Integr Cancer Ther

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Abstractl-Glutamine (l-GLN) is considered a nonessential amino acid that has a variety of applications in naturopathic medicine. It has been postulated that in the critically ill patient, GLN becomes an essential amino acid for recovery, restoration, and repair at a cellular level. Mucositis is an intestinal mucosal damage of the gastrointestinal tract-mouth, throat, stomach, intestines, rectum, and anus-that is caused directly by chemotherapies and radiotherapies. Cancer cachexia is a significant biochemical event, which is characterized by weight loss, fatigue, and indicative of depletion of skeletal muscle GLN-a hypercatabolic state. There has been some question as to the use of GLN in this patient population because of its role as a preferred energy source not only for enterocytes and lymphocytes but for malignant cells as well. This article will address the questions of safety, efficacy, dosing, and toxicity of GLN used as an integrative therapeutic in ongoing integrative cancer treatment.

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Glutamine Suppresses PGE2 Synthesis and Breast Cancer Growth

Cited by 48 publications

References 4 publications

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

Toward a Core Nutraceutical Program for Cancer Management

L-Glutamine Use in the Treatment and Prevention of Mucositis and Cachexia: A Naturopathic Perspective

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