Anti-cancer effects of high-dose selenium via lipid peroxidation in ovarian cancer.

person Jung-A Choi Gangnam Severance Hospital, Seoul, South Korea info_outline Jung-A Choi, Elizabeth Hyeji Lee, Hyosun Kim, Hanbyoul Cho, Jae-Hoon Kim

Authors person Jung-A Choi Gangnam Severance Hospital, Seoul, South Korea info_outline Jung-A Choi, Elizabeth Hyeji Lee, Hyosun Kim, Hanbyoul Cho, Jae-Hoon Kim Organizations Gangnam Severance Hospital, Seoul, South Korea, Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul, South Korea Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Selenium is an essential trace element and act as a regulator in the oxidation-reduction system. Selenium deficiency is observed in various cancers. Therefore, we investigated the relevance of high-dose selenium with the anticancer effect of ovarian cancer. Methods: We evaluated cytotoxicity and cell death by MTT assay and Annexin V-FITC/PI-labeled flow cytometry and biological function by invasion assay, ROS assay, immunoblotting, and FACS analysis. Using SKOV3-bearing xenograft mouse models, we evaluated the anti-cancer effect of high-dose selenium. Selenium toxicity was evaluated by the amount of ALT, AST, BUN and creatinine in the serum of C57BL/6 mice. Results: We observed that high-dose selenium, which was exposed to ovarian cancer cells, significantly increases the generation of reactive-species oxygen (ROS), leading to more significant cell death and cytotoxicity compared to low doses. We found that high-dose selenium triggers lipid peroxidation-mediated cell deaths and causes a reduction of glutathione peroxidase (GPX) systems. As a result of examining the lethal dose of selenium to the C57BL/6 nude mouse, it occurred in the concentration range of 3000 μg/Kg or more. SKOV3-bearing mouse models revealed the high-dose selenium administration (2000 μg/Kg) significantly reduced the ovarian tumor growth (p < 0.05). Moreover, we confirmed that high-dose selenium inhibited the expression of increased GPX in SKOV3-bearing mice. Conclusions: Our results suggest that high-dose selenium induces an anticancer effect through lipid peroxidation regulation according to the GPX redox system. Furthermore, we can suggest that chemotherapy based on high-dose selenium may have the effect of maximizing therapeutic efficacy and reducing anticancer drug resistance in ovarian cancer.