Redox active selenium (Se) compounds have gained substantial attention in the last decade
as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and
sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active
metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel
CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active
(GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action
of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl
derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds
was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell
detachment through downregulation of cell division control protein 42 homolog (CDC42) and its
downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds
have been reported to induce this type of cell death and is of importance in the characterization of
the anticancerogenic properties of these compounds
