N-Acetylcysteine Augments Surface Thiols and Differentially Modulates Cell Adhesion and Invasion in vitro and Metastatic Potential in vivo of B16F1 Melanoma

The redox state of surface protein thiols influences a variety of cell functions, and we recently reported that adhesion molecules can be redox regulated. We investigated the effect of reducing surface thiols using N-acetylcysteine (NAC) on the biological properties of murine melanoma B16F1 cells. Treating the cells with NAC (5mM for 2h, then removed by washing) augmented their capacity to adhere to fibronectin, as well as to adhere to and invade an endothelial cell monolayer. This was associated with an augmented expression of reduced surface protein thiols. However, when control or NAC-pretreated melanoma cells were injected i.v. in mice to induce experimental lung metastases, we could observe an inhibition of metastatic potential by NAC. This discrepancy suggest that other redox sensitive steps, in addition to adhesion, are important in regulating the metastatic phenotype in vivo.