Table 1 Diverse actions of NO in cancer: tumor promoting role of NO

Formation of toxic and mutagenic species

Direct modification of DNA– strand breaks, oxidation and deamination of nucleic acids

Inhibition of systems required to repair DNA lesions

GC to AT mutations in p53– loss of its repressor activity

Direct inhibition of caspase activity through s-nitrosylation of the cysteine thiol

Inhibition of cytochrome C release

Increase in Bcl-2 expression

Suppression of ceramide generation

Activation of cyclooxygenase

Dilatation of arteriolar vessels by eNOS

VEGF release and NO stimulation of hyperpermeability of vascular endothelium

Increased production of PGE2 resulting in increased tumor vasculature permeability

Activation of COX-2 which stimulates production of proangiogenic factors and prostaglandins

Suppression of proliferation and infiltration of leukocytes

Low leukocyte-endothelial interaction

Promotes lymphangiogenesis and spread to lymph nodes possibly through involvement of VEGF-C

Upregulation of MMP-2 and −9

Downregulation of TIMP-2 and-3