Exogenous hydrogen sulfide donor NaHS alleviates nickel-induced epithelial-mesenchymal transition and the migration of A549 cells by regulating TGF-β1/Smad2/Smad3 signaling.

Nickel compounds are known to be common environmental and occupational carcinogens which also promote the migration of lung cancer cells. However, the molecular mechanism yet remains to be clarified. Hydrogen sulfide (HS) is involved in cancer biological processes. However, the exact effect and functionality of HS on nickel, towards the promotion of the migration ability of lung cancer cells, remains to be unknown. In this study, we have found that the nickel chloride (NiCl) treatment significantly downregulates the protein levels of endogenous HS enzyme cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-Mercaptopyruvate sulfurtransferase (3-MST). A correlation between NiCl-induced epithelial-mesenchymal transition (EMT) and the migration ability of lung cancer A549 cells has been observed. Exogenous HS donor, sodium hydrogen sulfide (NaHS) (100 μmol/L), can reverse NiCl-induced EMT as well as the migration ability of A549 cells. NiCl treatment is able to upregulate the protein level of transforming growth factor-β1 (TGF-β1), p-Smad2, p-Smad3, p-JNK, p-ERK and p-P38 in a time-dependent fashion, indicating that both TGF-β1/Smad2/Smad3 and mitogen-activated protein kinase (MAPK) signaling cascades (a non-Smad pathway) may play essential roles in NiCl-dependent EMT as well as cell migration of human lung cancer cells. Furthermore, exogenous NaHS alleviates the NiCl-induced EMT and the migration ability of A549 cells only by regulating TGF-β1/Smad2/Smad3, rather than the MAPK, signaling pathway. These results indicate that the exogenous administration of NaHS might be a potential therapeutic strategy against nickel-induced lung cancer progression.