Table 1.

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

Tumor promoting role
Role of nitric oxide (NO)	Mechanism by which NO acts
Genotoxicmechanisms	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
Antiapoptotic effects	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
Induces and promotes angiogenesis (iNOSandeNOS)	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
Limits host immune response against tumor	Suppression of proliferation and infiltration of leukocytes
	Low leukocyte-endothelial interaction
Promotes metastasis	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