Effect of Vitamin D on Rad51 and NBS1 in Head and Neck Squamous Cell Carcinoma

Squamous cell carcinoma of the head and neck (HNSCC) is a common human cancer that affects 600,000 new patients each year, with high morbidity, high morality, and treatment options include surgery, chemotherapy, or radiation. Overexpression of Rad51 in human tumor cells, such as HNSCC, leads to increase genomic stability and resistance to DNA double-strand breaks induced by chemotherapy and radiation, allowing for continued cell proliferation. In human cells, there are two pathways to repair DNA double-strand breaks, non-homologous end-joining (NHEJ) and recombinational repair. Normally, Rad51 helps repair damaged DNA by homologous recombination. NBS1 is a key protein in NHEJ that binds to Rad51 bringing it to damaged DNA sites for homologous recombination. NBS1 has also been implicated as a prognostic marker for HNSCC. Vitamin D3 (VD3) is known to suppress cell proliferation, induce apoptosis and cell cycle arrest in HNSCC. This work used samples from hamster buccal pouch treated with a carcinogenic agent (7,12-dimethylbenz[a]anthracene; DMBA) to induce tumor formation, and VD3. Hamster buccal pouch tumors give an accurate comparison of the changes in the epithelium to the development of the human carcinoma. These hamster buccal pouch samples were stained for Rad51 and NBS1 proteins using immunohistochemistry techniques. To date, this work has shown that VD3 decreases the expression of Rad51 in these tissues similar to its effect on HNSCC in vitro. The elucidation of the expression of proteins in this pathway may be useful for the development of alternate therapeutic treatments for human HNSCC