Biochemie und Pharmakologie: Offener Zugang
Offener Zugang

Abstrakt

Mono-Methyl Selenium and Cancer Therapy: Current Status and Future Translational Research Needs

Barrow K, Jiang C and Lü J

The human clinical trials with seleno-methionine (SeMet) for prostate cancer prevention and selenized-yeast (contains mostly SeMet) for the prevention of non-small cell lung cancer and prostate cancer in North America conclusively rejected the use of these selenium (Se) forms for cancer prevention in human populations with adequate Se intake. Nevertheless, solid mechanism-based preclinical studies with other Se forms have suggested the potential for their use at pharmacological doses as adjuvant treatment alone and especially as chemo-enhancers for combination cancer therapy. Of the distinct pools of Se metabolites, the mono-methylated Se (MM-Se) has many desirable attributes for cancer therapy, affecting a multitude of crucial molecules and signaling pathways in cancer epithelial cells, vascular endothelial cells and microenvironment. Inorganic selenite/selenide in excess of selenoprotein synthesis can lead to DNA single strand breaks, which implicate possible genotoxicity to normal cells and are therefore unattractive for longterm use. In this paper, we review animal studies with MM-Se such as methylseleninic acid and Se-methylselenocysteine as well as inorganic Se for inhibition of xenograft tumors of several organ sites as single therapy and those using MMSe to enhance the therapeutic efficacy of cancer chemotherapeutic drugs and to reduce the dose-limiting toxicities of such modalities. We present and critique potential mechanisms of action for such applications and future improvement. Since Se-methylselenocysteine was the only MM-Se with a published human pharmacokinetic study, we discuss future research directions to enable clinical translation studies.