Antitumor Effects of Selenium

Abstract

Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 μg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients.

Keywords: ROS; apoptosis; metastasis; selenium compounds; treatment of advanced cancer patients.

Figure 1

Selenium metabolism.

Figure 2

Production of ROS by selenium.

Figure 3

Absorption mechanism of high dose of sodium selenite.

Figure 4

High doses of sodium selenite in treatment of advanced metastasis cancer patients. Case 1: Findings of abdomino-pelvic CT before (A) and after (B) the multidisciplinary treatment for a 51-year-old patient diagnosed with advanced stage ovarian cancer. Case 2: Findings of abdomino-pelvic CT before (C) and after (D) the integrative treatment for a 48-year-old patient diagnosed with recurrent ovarian cancer after primary intensive pelvic surgery with adjuvant chemotherapy, since 2017. Peritoneal carcinomatosis with massive ascites (A) and no evidence of disease (B) after 18 months of chemotherapy, interval debulking surgery, and PARP inhibitor maintenance therapy with high dose sodium selenite treatment according to regimen of Table 1 (SIMCH). Metastatic para-aortic lymph nodes with 12 cm-sized port site metastatic mass at left lower abdominal wall was noted (C), and no evidence of disease at left lower abdomen and stable disease of metastatic lymph nodes (D) after 16 months of metastatectomy of abdominal wall and maintenance immune checkpoint inhibitor (pembrolizumab) with high dose sodium selenite treatment according to regimen of Table 1 (SIMCH).