The downstream product of COX 2 enzymatic activity is prostaglandin E2, which serves as an essential stimulus for induction of several cell signaling pathways, including the NF W route that consequently regulates motility and cell growth. Indeed, inhibition of COX 2 enzymatic activity by specific pharmacological inhibitors is an effective instrument for controlling both infection and, sometimes, cancer growth. In recent publications, the others and we have proposed numerous natural product libraries different techniques for improving melanoma response to anticancer treatment. These generally include reduction of NF B activity by sodium arsenite treatment or by overexpression of the firm NF B inhibitor IBN, mixed treatment with sodium arsenite and EGFR inhibitors, selective inhibition of transcription factor ATF2 activation by the cognate peptide competitor, overexpression of transfected FasL in Fas positive melanomas and upregulation of the outer lining Fas receptor levels in metastatic melanomas. Reduction of inhibition of the PI3K AKT pathway and the NF Bdependent term of success proteins have been related to a remarkable increase in the awareness of cancer cells to endogenous TNF and TRAIL. The aim of the current study was to check whether recovery of endogenous surface expression of FasL in Fas good melanomas could aid apoptosis of these cancer cells. We discovered that the combined treatment of cancer cells with sodium arsenite and NS398, an of Urogenital pelvic malignancy COX 2, will be an effective tool for induction of cancer cell apoptosis. Surprisingly, such combined treatment didn’t stimulate FasL transcription and the FasL promoter action in melanomas but substantially affected FasL translocation and expression on the cell surface. Sodium arsenite and cycloheximide were obtained from Sigma. NS398, a inhibitor of COX 2, was purchased from Cayman Chemical Company. Tumefaction necrosis factor alpha was purchased from Roche, recombinant human IL 1B was received from R&D Systems. Individual soluble Fas Ligand was obtained from Alexis. BD Cytofix/Cytoperm system was obtained from BD Pharmingen. Caspase inhibitors zVAD Ac LEHD CHO, Ac fatty acid amide hydrolase inhibitors IETD CHO and fmk were purchased from Calbiochem. MMP inhibitor II, matrix metalloproteinase inhibitors GM1439 and MMP inhibitor III were obtained from Calbiochem. Pre throw SDS polyacrylamide fits in were purchased from BioRad. Human cancer cell lines WM793, SBcl2, LU1205, WM9, WM35 and OM431 were managed in DMEM medium supplemented with 10% fetal bovine serum, M glutamine and antibiotics. HHMSX, femx and LOX, human cancer lines were maintained in RPMI1640 medium supplemented with ten percent FCS and antibiotics. Normal human melanocytes were obtained from the Department of Dermatology, Yale University and managed in TICVA method for normal human melanocytes, as suggested by the manufacturer.