Table 3.

In vivo and in vitro preclinical studies involving NO donors.

In Vivo Preclinical Studies
NO Drug	Cancer Type	Additional Treatment	Effect	Reference
Isosorbide mononitrate (ISMN) and isosorbide dinitrate (ISDN)	Lewis Lungcarcinoma in mice	None	Inhibited angiogenesis and tumor growth	[241]
Nicorandil	Sprague-Dawley rats without malignancy	Bleomycin	Reduced lung inflammation and fibrosis	[242]
DETA/NO	BALB/c female mice with mammary adenocarcinoma in a experimental metastasis model	CORM-A1	Inhibited the EMT	[243]
PROLI/NO	Sprague–Dawley rats with Brain Gliomas	Carboplatin	Increased blood brain barrier permeability and survival	[239]
S-nitrosoglutathione	Mouse xenograft model with head and neck squamous cell carcinoma	Radiation and cisplatin	Decreased tumor growth and enhanced therapySTAT3 inhibition	[244]
S-nitrosoglutathione	C57BL/6J mice with castration resistant prostate cancer	None	Decreased tumor burdenIncreased the expression of LH, FSH, and testosteroneDecreased M2 TAM and increased T1 TAMAndrogen receptor downregulation	[182]
In Vitro Preclinical Studies
NO Drug	Cancer Type	Additional Treatment	Effect	Reference
ω-hydroxy-L-arginine	MDA-MB-468 Breast Cancer Cells	None	Decreased cellular proliferative and Increased apoptosis	[245]
isosorbide mononitrate	HCT116 and SW620 colon cancer cells	Aspirin	Synergistic effect of therapy on inhibition of cell growth	[246]
Sodium Nitroprusside/L-arginine	AGS gastric cancer cell line	None	Inhibition of Epidermal growth factorActivation of type II cGMP-dependent protein kinase	[247]
Sodium Nitroprusside	SGC-7901, AGS, MKN45 and MKN28 gastric cancer cells	None	Increased apoptosis through TRAIL cytotoxicity	[248]
Sodium Nitroprusside	TSCCa tongue oral squamous cell carcinoma	None	Concentration-dependent cytotoxicity and increased apoptosis	[249]
Sodium Nitroprusside	N1E-115 neuroblastoma cells	Cycloheximide	Induction of cell death	[250]
Sodium Nitroprusside	HeLa cervical cancer cells	GS28 siRNA (siGS28) transfection	Inhibited cytotoxic responseIncreased ERK	[251]
Sodium Nitroprusside	HepG2 and Hep3B Hepatocellular carcinoma cells	Deferoxamine	Induced apoptosisApoptoic effect inhibited by deferoxamine pretreatment	[252]
Sodium Nitroprusside	Eight human pancreatic tumour cell lines	Radiation	Increased sensitivity to radiotherapy	[253]
Sodium Nitroprusside	SK-MEL-28 and WM793 Melanoma Cell Lines	Arginine Deprivation	Increased therapeutic effect	[254]
Sodium Nitroprusside	SH-SY5Y neuroblastoma cells	2-day light-exhausted compound SNP(ex)	Increased apoptosisIncrease in p53 activation of both SNP and SNP(ex)	[255]
S-nitroso-N-acetylpenicillamine and sodium nitroprusside	CHP212 neuroblastoma cells	Deferoxamine	Induced apoptosis, although with a different time to inhibition.	[256]
ruthenium nitrosyl complex trans-[Ru(NO)(NH3)4(py)](PF6)3]	HepG2 Liver cancer cells	None	Induced apoptosis	[239]
Spermine nitric oxide complex hydrate (SPER/NO)/ diethylenetriamine nitric oxide adduct (DETA/NO)	SK-OV-3 and OVCAR-3 ovarian cancer cell	None	Enhanced cytotoxicity and inhibited apoptosisDownregulation of STAT3 and AKT	[249]
DETA-NONOate	MDA-MB-231 breast cancer cells	None	Induced G1 phase growth arrestDownregulation of cyclin D1Hyperphosphorylation of RB	[257]
DETA-NONOate	MDA-MB-468 breast cancer cells	Farnesyltransferase inhibitor	Induced apoptosisCytochrome-c release and caspase 3/9 activation	[236]
DETA-NONOate	MDA-MB-231, MDA-MB-157, MDA-MB-436, HCC-1806, HCC-70, MDA-MB-468, HCC-1395 and BT-549 breast cancer cell	None	Increased mitochondrial induced apoptosis in African American cancer cell lines but not caucasian cells lines	[258]
DETANONOate	DU145 and PC-3 Prostate cancer cells	None	Prevented the EMTSNAIL/EMK inhibition	[240]
SNAP and DETA-NONOate	Myeloid derived suppressor cells	None	Inhibited cancer antigen presentation to CD4+ T cells	[259]
Sodium nitroprusside, S-nitroso-N-acetylpenicilamine, S-nitrosoglutathione, (+/−)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide, and iNOS transfection	PC-3MM2, LNCaP, and DU145 prostate cancer cells	NO scavengers	Inhibited TGF-B productionSodium nitroprusside and iNOS transfection were ablated with the NO scavengers	[260]
S-nitrosoglutathione	HCT116 and SW620 colon cancer cells	None	Increased apoptosisActivation of ERK1/2 and p38 kinase	[261]
S-nitrosoglutathione	MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 cell lines and AGS cells	U0126 MEK Inhibitor	Growth inhibition through EGFR, IGF-1, and AKT signallingGrowth inhibition increased with U0126 MEK inhibitor	[262]
S-nitrosoglutathione	A549 and NCI-H1299 lung cancer cells	None	Growth inhibition via Prdx2 and AMPK	[263]