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

Valentina K. Todorova, Stacy A. Harms, Yihong Kaufmann, Shaoke Luo, Kevin Q. Luo, Kirk Babb, Vicki Klimberg

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalBreast Cancer Research and Treatment
Volume88
Issue number3
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Bax
  • Bcl-2
  • Caspase-3
  • DMBA-breast cancer model
  • Glutamine
  • Glutathione

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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