Therapeutic Potential of Selenium Compounds in the Treatment of Cancer
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The potential applications of different selenium compounds as cancer chemotherapeutic agents is an active area of research within the field of cancer drug discovery. The antineoplastic efficacies of many of these small molecules have been extensively investigated, mainly in multiple preclinical models of cancer. Sodium selenite and Se-methylselenocysteine represent two of such selenium compounds, the cytotoxic and antiproliferative efficacies of which are discussed herein. These compounds differ in their mechanisms of action. Sodium selenite exerts its cytotoxic effects by directly oxidizing cellular free thiol pools. In contrast, Se-methylselenocysteine undergoes enzymatic transformation into methylselenol which is cytotoxic due to its ability to redox cycle with cellular thiols. Despite the inherent differences in their metabolic transformations, the disruption of the cellular redox balance and the activation of pro-death intracellular signaling pathways have been implicated as the most prevalent mechanisms of their cytotoxic effects. Both of these selenium compounds exert synergistic toxic effects with certain cancer chemotherapeutics. Together, the well-documented tumor-specific cytotoxic and antiproliferative effects of these compounds have paved the path for their clinical translation. In a phase I clinical trial, it has been shown that sodium selenite is well tolerated in human up to a dose of 10.2 mg/m2 when administered daily for 5 days a week for 2 weeks. Similarly, Se-methylselenocysteine exhibits a favorable pharmacokinetic and safety profile during prolonged oral administration in healthy subjects. Further studies are warranted to investigate their cancer chemotherapeutic efficacies in clinical settings.
KeywordsCancer Sodium selenite Se-methylselenocysteine Selenium metabolism Phase I clinical trial Chemotherapeutic agents
The authors would like to thank financial support from Barncancerfonden, Cancerfonden, Cancer- och Allergifonden, KI Fonder, Jochnick Foundation, Radiumhemmetsforsknings fonder, and the County Council of Stockholm.
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