Combination radiation and chemotherapy are commonly used to treat locoregionally advanced head and neck squamous cell carcinoma. Aggressive dosing of these therapies is significantly hampered by side effects due to normal tissue toxicity. Selenium represents an adjuvant that selectively sensitizes cancer cells to therapy, potentially by inducing lipid peroxidation (LPO). This study investigated whether one such selenium compound, methylseleninic acid (MSA), induces LPO and radiation sensitivity in HNSCC cells. Results from BODIPY C11 oxidation and ferric thiocyanate assay revealed that MSA induced LPO in HNSCC cells rapidly and persistently. Cell counts and propidium iodide viability assays showed that MSA was more toxic to HNSCC cells than other related selenium compounds, and this toxicity was abrogated by treatment with α-tocopherol, an LPO inhibitor. MSA was also found to sensitize HNSCC cells to radiation by clonogenic assay. The addition of MSA to a cell-free solution of glutathione (GSH) resulted in an increase in oxygen consumption as measured by Clark electrode, suggesting the formation of reactive oxygen species. Intracellular GSH in HNSCC was depleted following MSA treatment. Supplementation of the intracellular GSH pool with N-acetylcysteine (NAC) rendered the cells more sensitive to MSA. Results from this study identify MSA as an inducer of LPO, and reveal its capability to sensitize HNSCC to radiation. MSA may represent a potent adjuvant to combination therapy in HNSCC.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-7023 |
| Date | 01 May 2017 |
| Creators | Lafin, John Thomas |
| Contributors | Goswami, Prabhat C. |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | dissertation |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright © 2017 John Thomas Lafin |
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