Sulforaphane-cysteine-induced apoptosis via phosphorylated ERK1/2-mediated maspin pathway in human non-small cell lung cancer cells.

Sulforaphane (SFN) was demonstrated to induce apoptosis in a variety of cancers via multiple mechanisms. However, owing to a short half-life in circulation, SFN was not used for clinical treatment yet. Interestingly, SFN analog, sulforaphane-cysteine (SFN-Cys) has a longer half-life in metabolism, and we previously demonstrated that SFN-Cys inhibited invasion in human prostate cancer cells. Here, we would investigate whether SFN-Cys induces apoptosis and find the underlying mechanisms in human non-small cell lung cancer (NSCLC) cells. Western blots were used to test the molecular linkages among extracellular signal-regulated kinases 1/2 (ERK1/2) and downstream signal molecules. Flow cytometry and fluorescence microscopy were used to detect cell death. Cell proliferation assay showed that SFN-Cys inhibited cell viability following a dose-dependent manner. Abnormal cell morphology was viewed after the cells were exposed to SFN-Cys. Flow cytometry showed that SFN-Cys induced cell apoptosis via a dose-dependent manner. Further, SFN-Cys triggered the activation of ERK1/2, which resulted in the upregulation of maspin, Bax, cleaved caspase-3 and downregulation of pro-caspase-3, Bcl-2, -tubulin. Meanwhile, we demonstrated that recombinant caspase-3 cleaved -tubulin in the lysate of cells, which were treated by SFN-Cys. These data indicated that SFN-Cys activated the ERK1/2-mediated mitochondria signaling pathway with maspin upregulation and -tubulin downregulation leading to apoptosis. These findings will help to develop a novel therapeutic to target NSCLC cells.