Portal de Periódicos da CAPES

Cadmium in human pancreatic cancer – preliminary report

2016; Elsevier BV; Volume: 258; Linguagem: Inglês

10.1016/j.toxlet.2016.06.1406

1879-3169

Vladimir Djordjević, Dejan Knezevic, Slavko Matić, Mirko Kerkez, Nemanja Zaric, Nikola Grubor, Nemanja Bidzic, Novica Boričić, Ivan Boričić, Vesna Matović, Aleksandra Buha Djordjević,

Biocrusts and Microbial Ecology

Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer cells. However, the roles of MC-LR in regulating epithelial-mesenchymal transition (EMT) in colorectal cancer cells remain unknown. In our study, we observed that MC-LR treatment decreased epithelial marker E-cadherin expression and up-regulated the levels of mesenchymal markers Vimentin and Snail in colorectal cancer cells. Moreover, MC-LR stimulated protein expression of SMAD2 and phospho-SMAD2 by PI3-K/AKT activation. The activated PI3-K/AKT and SMAD2 signaling largely accounted for MC-LR-induced EMT, which could be reversed by SMAD2 RNA interference or PI3-K/AKT chemical inhibitor in colorectal cancer cells. Our results show that MC-LR could induce SMAD2 expression to promote colorectal cancer cells EMT, which not only provides a mechanistic insight on MC-LR promotes EMT in colorectal cancer cells, but also support to the development of therapies aimed at SMAD2 in colorectal cancer induced by MC-LR.