Selenium Cytotoxicity in Cancer

Abstract

Selenium is an essential trace element with growth-modulating properties. Decades of research clearly demonstrate that selenium compounds inhibit the growth of malignant cells in diverse experimental model systems. However, the growth-modulating and cytotoxic mechanisms are diverse and far from clear. Lately, a remarkable tumour selective cytotoxicity of selenium compounds has been shown, indicating the potential of selenium in the treatment of cancer. Of particular interest are the redoxactive selenium compounds exhibiting cytotoxic potential to tumour cells. These selenium compounds elicit complex patterns of pharmacodynamics and pharmacokinetics, leading to cell death pathways that differ among compounds. Modern oncology often focuses on targeted ligand-based therapeutic strategies that are specific to their molecular targets. These drugs are initially efficient, but the tumour cells often rapidly develop resistance against these drugs. In contrast, certain redox-active selenium compounds induce complex cascades of pro-death signalling at pharmacological concentrations with superior tumour specificity. The target molecules are often the ones that are important for the survival of cancer cells and often implicated in drug resistance. Therefore, the chemotherapeutic applications of selenium offer great possibilities of multi-target attacks on tumour cells. This MiniReview focuses on the tumour-specific cytotoxic effects of selenium, with special emphasis on cascades of cellular events induced by the major groups of pharmacologically active selenium compounds. Furthermore, the great pharmacological potential of selenium in the treatment of resistant cancers is discussed.

Serum Levels of Selenium and Zinc in Patients with Breast Cancer: A Case-Control Study

“…The vital elements such as copper, Zn, and Se are connected together in cytosolic defense against reactive oxygen and nitrogen species (18). Human and laboratory studies have been conducted on the role of these 2 elements in preventing carcinogenesis process and tumor cell growth (19)(20)(21)(22). On the other hand, epidemiological studies have shown that differences in dietary habits or diet (23,24) and air pollution (25) can effect on risk of BC, in line with genetics (26).…”

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae*

“…Most probes used for the determination of superoxide ions are not specific and can react with other species (11). For example, nitroblue tetrazolium reacts with selenolate anions in the absence of dioxygen 3 and therefore cannot be used to monitor superoxide production. To indirectly demonstrate the production of superoxide during selenol oxidation, we studied the effect of SOD on the rate of the auto-oxidation reaction.…”

“…At supranutritional levels, there are indications that selenium has anticarcinogenic and disease preventing properties. However, at higher doses selenium compounds are toxic, and the gap between toxic and prophylactic or therapeutic doses is narrow (2,3). Numerous studies were performed to evaluate the toxic effects of different forms of selenium, either organic, such as selenomethionine (SeMet), or inorganic, such as selenite.…”

Fusarium oxysporum, a bio-Factory for Nano Selenium Compounds: Synthesis and Characterization

“…Moreover, in approximately all organic and inorganic sulfur compounds, selenium can substitute sulfur [21].…”