Potential of Selenium Compounds as New Anticancer Agents for Cholangiocarcinoma

Abstract

We examined the in vitro effects of the selenium compounds sodium selenite (Se) and selenomethionine (SeMet) on cholangiocarcima (CCA) cell growth and migration to determine their potential usefulness as anticancer agents. The effect of both compounds on the selenoprotein M level was investigated, as well as the association between the expression level of selenoprotein M and the patients' clinicopathological data. Se and SeMet inhibited CCA cell growth with half-maximal inhibitory concentration values of 1.7-2.1 μM and 18.8-37.9 μM, respectively. Both compounds increased the ratio of B-cell lymphoma 2 (BCL2) to BCL2-associated X (BAX), triggering apoptotic cell death, and inhibited cell migration by reducing the ratio of N-cadherin to E-cadherin, an epithelial-mesenchymal transition marker. In addition, Se and SeMet increased selenoprotein M protein in CCA cells. Low expression of selenoprotein M in CCA tissues was significantly associated with shorter patient survival. In conclusion, selenium may potentially be an alternative anticancer agent that might lead to a better prognosis in patients with CCA.

A Summary of New Findings on the Biological Effects of Selenium in Selected Animal Species—A Critical Review

“… Physiological effects of selenium. Selenium is known for its antioxidant, antimutagenic and anticarcinogenic properties, it also acts against microbes as well as parasites and has antiinflammatory effects, engages in metabolism, growth and development, protects organs from oxidative stress, affects immune function and improves fertility [ 2 , 47 , 48 , 49 , 50 , 53 , 54 , 60 , 82 , 87 , 104 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. …”

Selenoproteins in Tumorigenesis and Cancer Progression

“…This particular allele is associated with increased risk of breast and head and neck cancers in African Americans, although among smokers, those harboring a GG or GA1125 variant were at higher risk for lung cancer than those with AA1125 (Hu et al, 2001;Jablonska et al, 2008). SELENOF is a functional homolog of SELENOM (Reeves and Hoffmann, 2009), which is downregulated in cholangiocarcinoma and low expression is correlated with worse prognosis (Dai et al, 2016). However, SELENOM's functional contribution to tumorigenesis remains largely unknown.…”

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

“…Invasion and metastasis are considered as complex processes involving detachment of cancer cell from primary tumour site and formation of new tumour foci in distant organs . Epithelial‐mesenchymal transition (EMT), a developmental regulatory programme, identified as transformed epithelial cells loss epithelial constraints and then acquire the abilities to invade, resist apoptosis and metastasis, which is believed to play a vital role in broadly regulating invasion and metastasis . Cadherins are a family of calcium‐dependent glycoproteins, which responsible for Ca 2+ ‐dependent cell‐cell adhesions.…”

“…[3][4][5] Epithelial-mesenchymal transition (EMT), a developmental regulatory programme, identified as transformed epithelial cells loss epithelial constraints and then acquire the abilities to invade, resist apoptosis and metastasis, which is believed to play a vital role in broadly regulating invasion and metastasis. 2,[6][7][8][9] Cadherins are a family of calcium-dependent glycoproteins, which responsible for Ca 2+ -dependent cell-cell adhesions. Of the members of this family, N-cadherin (neuronal cadherin or cadherin-2), a transmembrane glycoprotein, which is normally expressed in neuroectodermal and mesenchymal-derived tissues, plays crucial role in lots of processes, such as cell-cell adhesion, embryogenesis, gastrulation, neurulation, migration and invasion.…”