Glutamine prevents DMBA-induced squamous cell cancer

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.