Nitric Oxide and Cancer Development

Abstract

Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

β-Selinene-Rich Essential Oils from the Parts of Callicarpa macrophylla and Their Antioxidant and Pharmacological Activities

“…The scavenging effect of the EOs and standards with the DPPH radical were observed in the following order: gallic acid (IC 50 = 7.95 ± 0.11 µg/mL) > catechin (IC 50 = 8.18 ± 0.11 µg/mL) > BHT (8.55 ± 0.10 µg/mL) > CMEO-II (IC 50 =15.66 ± 0.03 µL/mL) > CMLEO (IC 50 =18.35 ± 0.18 µL/mL) > CMEO-I (IC 50 = 20.19 ± 0.11 µL/mL). It has been reported earlier that the plant-derived products mitigate the harmful effects produced by nitric oxide radicals in human body [20,21]. In the present investigation, the level of nitric oxide was decreased with increased concentration of the EOs.…”

“…In this activity, the animals were treated with glacial acetic acid intraperitoneally to induce pain sensation [21]. After 1 h, 0.2 mL of EOs, ibuprofen (40 mg/kg b.…”

Anti-Cancer Activity of Nitrones and Observations on Mechanism of Action

“…Isolated hepatocytes from rats receiving the normal diet did not produce NO. We also showed, using the NO trapping agent methylglucamine dithiocarbamate and real-time electron paramagnetic resonance, that the bile flowing from the liver of live animals on the choline deficient diet produced NO but those on a normal diet produced significantly less if any NO [24]. Utilizing in situ fluorescent antibody staining we also found that PBN administration caused suppression of inducible nitric oxide synthase (iNOS) expression in the liver of rats fed the choline deficient diet.…”

“…When studying hepatocytes isolated from livers of rats administered the choline deficient diet we discovered that a significant portion of these cells produced nitric oxide (NO) and that PBN administration to the rats caused suppression of the production of NO [23, 24]. In addition administering the nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine as well as aminoguanidine in the diet caused suppression of NO production by hepatocytes, indicating that the NO produced was dependent on the activity of NOS.…”

“…We have recently written an extensive review on this research area [24] and therefore will only provide the basic conclusions reached to explain our results. First, there are many observations in several different models clearly showing that NO production at moderate levels enhances cancer development.…”