The Regulation of Pathways of Inflammation and Resolution in Immune Cells and Cancer Stem Cells by Selenium

Abstract

Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override anti-proliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of pro-oxidant reactive oxygen and nitrogen species (RONS) can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis. Modulation of cellular metabolism in tumor cells as well as immune cells in the tumor microenvironment (TME) can impact inflammatory networks. Altering these pathways can potentially serve as a portal for therapy. It is well known that selenium, through selenoproteins, modulates inflammatory pathways in addition to regulating redox homeostasis in cells. Therefore, selenium has the potential to impact the interaction between tumor cells, cancer stem cells, and immune cells. In the sections below, we review the current status of knowledge regarding this interaction, with reference to leukemia stem cells (LSCs), and the importance of selenium-dependent regulation of inflammation as a potential mechanism to affect the TME and tumor cell survival.

Selenium, Selenoproteins, and Immunity

“…However, how selenium levels affect macrophage polarization in the tumor microenvironment in human cancers remains to be determined. As discussed in a previous review [ 165 ], higher levels of selenium can increase NK cell activity by preventing the non-enzymatic formation of parafibrin that surrounds tumor cells and hinders immune surveillance and by activating the NK cell population in the tumor microenvironment. The anti-tumoral activity of NK cells requires the expression of the activating receptor natural killer group 2 member D (NKG2D) on NK cell surfaces [ 166 ].…”

Selenoproteome Identification in Inflamed Murine Primary Bone Marrow-Derived Macrophages by Nano-LC Orbitrap Fusion Tribrid Mass Spectrometry

“…× 50 cm) using a 0.1% formic/acetonitrile gradient at 300 nl/min. The mass spectrometer was set to collect one MS1 scan (Orbitrap; 120 K resolution; AGC target 2×10 5 ; max IT 100 ms) followed by data-dependent, "Top Speed" (3 s) MS2 scans (collision induced dissociation; ion trap; NCD 35; AGC 5×10 3 ; max IT 100 ms). For multinotch-MS3, the top ten precursors from each MS2 scan were fragmented by high-energy collisional dissociation (HCD) followed by Orbitrap analysis (NCE 55; 60,000 resolution; AGC 5×10 4 ; max IT 120 ms, 100-500 m/z scan range).…”

“…Decoding of the UGA stop codon by Sec tRNA [Ser]Sec leads to the specific incorporation of Sec within 25 (24 in mice) selenoproteins in humans [3]. The expression of these selenoproteins in macrophages is not only regulated by the bioavailability of Se, but also by pathways related to stress and inflammation that helps to reduce free radicals and efficiently restore redox homeostasis [4,5]. Inflammation is a cellular response to diverse extracellular stimuli leading to the release of plethora of mediators, which is sequentially followed by resolution [6], where macrophages play a dual role.…”

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

“…Selenite is able to oxidize these free and protein-bound sulfhydryl groups to corresponding disulfides, which inhibits the protective (parafibrin-) barrier of cancer cell membranes and make them vulnerable to the destructive activity of phagocytes [4,5]. In addition, selenite causes an increase of immunocompetent cells like macrophages and can direct activate natural killer (NK) cells [4,6].…”