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Targeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits and anti-cancer activities exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. For the current study, we focused on molecular mechanisms by which MSA inhibited angiogenesis.
The effect of MSA on angiogenesis was evaluated in vitro, ex vivo and in vivo through the tube formation assay, the aortic ring assay and the chick chorioallantoic membrane model, respectively.
Herein, we demonstrate that MSA inhibited angiogenesis at 2μM, which falls in the range of moderate Se nutritional status. We found that MSA increased cell adherence, while inhibiting cell migration and tube formation in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin β3 at the levels of mRNA and protein, and disrupted the clustering of integrin β3. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB.
Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels by down-regulating and disorganizing the clustering of integrin β3, which further inhibited the phosphorylation signaling cascade involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy.