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Glutamine prevents DMBA-induced squamous cell cancer

V Lim1, S Korourian, V K Todorova

  • 1Department of Otolaryngology, University of Arkansas for Medical Sciences (UAMS), 4301 W. Markham Street, Mail Slot 725, Little Rock, AR 72205, United States.

Oral Oncology
|July 19, 2008
PubMed

Insights

Topical glutamine (GLN) application prevented oral cancer development in hamsters. GLN enhanced antioxidant status and promoted apoptosis, suggesting chemopreventive potential against oral squamous cell carcinoma.

Area of Science:

  • Oncology
  • Carcinogenesis
  • Molecular Biology

Background:

  • Oral squamous cell carcinoma (OSCC) etiology involves environmental carcinogens.
  • Previous studies linked oral glutamine (GLN) to inhibited breast cancer growth via host stimulation and tumor glutathione (GSH) inhibition.
  • GLN's effects included NK cell activity up-regulation, decreased IGF-1 and TGF-beta, and PI-3K/Akt pathway downregulation.

Purpose of the Study:

  • To investigate the chemopreventive effect of topically applied glutamine (GLN) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinoma.
  • To analyze histopathological changes, GLN and GSH levels, apoptosis-related protein expression, and gene mutations (H-ras, p53).

Main Methods:

  • DMBA was applied to induce buccal pouch tumors in hamsters.
  • Animals received topical GLN supplementation.
  • Histopathology, enzyme assays for GLN and GSH, Western blotting for bax, bcl-2, PARP, and DNA sequencing for H-ras/p53 mutations were performed.

Main Results:

  • None of the GLN-supplemented animals developed tumors, unlike all control animals.
  • GLN application increased arterial GLN and GSH, and buccal mucosa GSH.
  • Induction of bax and PARP, inhibition of bcl-2, and wild-type H-ras and p53 genes were observed.

Conclusions:

  • Topical GLN demonstrated significant chemopreventive effects against DMBA-induced oral cancer.
  • GLN's efficacy is associated with enhanced antioxidant status and apoptosis activation.
  • These findings support GLN's potential as a chemopreventive agent for oral squamous cell carcinoma.

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