Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells

• Published in: International journal of molecular sciences Vol. 20; no. 1; p. 225
• Main Authors: Lafin, John T, Sarsour, Ehab H, Kalen, Amanda L, Wagner, Brett A, Buettner, Garry R, Goswami, Prabhat C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.01.2019; MDPI
• Subjects: Acetylcysteine - pharmacology; Antitumor activity; Apoptosis - drug effects; Apoptosis - radiation effects; Biocompatibility; Cancer therapies; Cell death; Cell Line, Tumor; Chemotherapy; Enzymes; Fibroblasts; Gamma Rays; glutathione; Glutathione - metabolism; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipid Peroxidation - radiation effects; Lipids; Metabolites; methylseleninic acid; Organoselenium compounds; Organoselenium Compounds - pharmacology; Oxygen Consumption - drug effects; radiation; Radiation therapy; Radiation Tolerance - drug effects; Radiation Tolerance - radiation effects; Selenium; Squamous cell carcinoma; Superoxide; Thiols; Time Factors; tocopherol; Toxicity; Tumors; head and neck cancer; selenium; methylseleninic acid; radiation; glutathione; tocopherol; lipid peroxidation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010225

Combination radiation and chemotherapy are commonly used to treat locoregionally advanced head and neck squamous cell carcinoma (HNSCC). 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 these treatments modalities, 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 4,4-difluoro-4-bora-3a,4a-diaza- -indacene (BODIPY) C11 oxidation and ferric thiocyanate assays revealed that MSA induced LPO in cells rapidly and persistently. Propidium iodide (PI) exclusion assay found that MSA was more toxic to cancer cells than other related selenium compounds; this toxicity was abrogated by treatment with α-tocopherol, an LPO inhibitor. MSA exhibited no toxicity to normal fibroblasts at similar doses. MSA also sensitized HNSCC cells to radiation as determined by clonogenic assay. Intracellular glutathione in cancer cells was depleted following MSA treatment, and supplementation of the intracellular glutathione pool with -acetylcysteine sensitized cells to MSA. The addition of MSA to a cell-free solution of glutathione resulted in an increase in oxygen consumption, which was abrogated by catalase, suggesting the formation of H₂O₂. 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 radiation therapy in HNSCC.