Differential actions of selenium on Tumor vs. Normal increase radiosensitivity

Selenium is an essential trace element required for normal health and is also a promising agent for preventing cancer. In clinical trials, selenium has significantly protective effects against lung, prostate, colon, and head and neck cancer. Solid tumors in hypoxic and hypoxic/reoxygenation condition have long been considered a problem in cancer therapy. Hypoxic tumor cells were shown to be more resistant to radiotherapy (RT) and many conventional chemotherapeutic agents than their normoxic counterparts. Lung cancer is the leading cause of cancer death in both men and women in the United States. Non-small cell lung cancer (NSCLC) accounts for more than 75% of all lung cancers. RT is the routine treatment modality for these lung cancer patients. The goal of RT is to deliver cytotoxicity to the tumor site, while minimizing cytotoxicity to the surrounding normal tissues. Peroxiredoxin I (Prx I) has been reported to be highly elevated in lung cancer compared to that in normal tissues. NF-E2-related factor 2 (Nrf2) assumed as one of the major transcription factors of Prx I. Nrf2 plays a critical role in regulating expression of antioxidant and phase II drug-metabolizing enzymes, thereby contributing to detoxification, elimination, and protection of tissues or cells against environmental oxidative stress or xenobiotics including medicine. In the present study, we demonstrate that pretreatment with selenium has differential effect on tumor and normal tissue that might be associated with different regulation of Nrf2 under the circumstances of surrounding microenvironment