Nitric oxide (NO) is a lipophilic,highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including va sodilation,respiration,cell migration,immune resp onse and apoptosis.NO is synthesized by three differ entially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1),inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3).All isof or ms of NOS catalyze the reaction of L-arginine,NA DPH and oxygen to NO,L-citrulline and NADP.NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nit rosation) and tyrosine (nitration) residues,mixed disulf ide formation (S-nitrosoglutathione or GSNO) or prom ot ing further oxidation protein stages which have been related to altered protein function and gene transcription,genotoxic lesions,alteration of cell-cycle check points,apoptosis and DNA repair.NO sensitizes tumor cells to chemotherapeutic compounds.The expression of NOS-2 and NOS-3 has been found to be increased ina variety of human cancers.The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest,apoptosis or adaptation. Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including va sodilation, respiration, cell migration, immune resp onse and apoptosis. NO is synthesized by three differ entially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS- 2) and endothelial NOS (eNOS or NOS- arginine, NA DPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well by by cGMP-independent pathways including postranslational modifications in cysteine ​​(S-nitrosylation or S-nit rosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or prom otling further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair.NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation.