1-methylpropyl-2-imidazolyl-disulfide and Mouth-Neoplasms

The majority of cases of oral squamous cell carcinoma (OSCC) develop from oral potentially malignant disorders, which have been confirmed to be involved in chronic oxidative stimulation. However, no effective treatment approaches have been used to prevent the development of dysplasia into cancerous lesions thus far. In the present study, a well-established OSCC model was used to detect proteomics profiles at different stages during oral malignant transformation. Of the 15 proteins that were found to be upregulated in both the dysplasia and carcinoma stages, the oxidative stress-associated proteins, thioredoxin-1 (Trx-1), glutaredoxin-1 and peroxiredoxin-2 were note as the proteins with significant changes in expression Trx-1 was identified to be the most significantly upregulated protein in the precancerous stage. Validation experiments confirmed that Trx-1 was overexpressed both in dysplasia and cancerous tissue samples, and the inhibition of Trx-1 was able to promote the apoptosis of OSCC cells under hypoxic conditions. Furthermore, the experimental application of a Trx-1-specific inhibitory agent in an animal model led to a lower cancerization rate and a delay in tumor formation. The possible mechanisms were associated with the increased apoptosis via a reactive oxygen species (ROS)-dependent pathway. Taken together, our findings indicate that Trx-1 may be an important target for delaying oral malignant transformation, which provides a novel therapeutic strategy for the prevention and treatment of OSCC.

Topics: 4-Nitroquinoline-1-oxide; Adult; Aged; Animals; Apoptosis; Biomarkers, Tumor; Carcinogenesis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Transformation, Neoplastic; Disulfides; Female; Humans; Imidazoles; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasms, Experimental; Orthognathic Surgical Procedures; Oxidative Stress; Precancerous Conditions; Proteomics; Quinolones; Rats, Sprague-Dawley; Reactive Oxygen Species; Thioredoxins; Tongue