Nitroxyl as a Potential Theranostic in the Cancer Arena

Abstract

Significance: As one-electron reduced molecule of nitric oxide (NO), nitroxyl (HNO) has gained enormous attention because of its novel physiological or pharmacological properties, ranging from cardiovascular protective actions to antitumoricidal effects. Recent Advances: HNO is emerging as a new entity with therapeutic advantages over its redox sibling, NO. The interests in the chemical, pharmacological, and biological characteristics of HNO have broadened our current understanding of its role in physiology and pathophysiology. Critical Issues: In particular, the experimental evidence suggests the therapeutic potential of HNO in tumor pharmacology, such as neuroblastoma, gastrointestinal tumor, ovarian, lung, and breast cancers. Indeed, HNO donors have been demonstrated to attenuate tumor proliferation and angiogenesis. Future Directions: In this review, the generation and detection of HNO are outlined, and the roles of HNO in cancer progression are further discussed. We anticipate that the completion of this review might give novel insights into the roles of HNO in cancer pharmacology and open up a novel field of cancer therapy based on HNO. Antioxid. Redox Signal. 32, 331-349.

CO bonding in hexa‐ and pentacoordinate carboxy‐neuroglobin: A quantum mechanics/molecular mechanics and local vibrational mode study

“…Therefore, we have taken a different route by introduction an intrinsic bond strength measure based on the local vibrational mode analysis (LMA) 95 which has led to the metal electronic parameter (MLEP), for quantifying a M‐L bonding, 96,97 which was shown to be superior to the more qualitative Tolman electronic parameter (TEP) 98,99 . In two recent pilot studies applying a hybrid QM/MM (quantum mechanics/molecular mechanics) methodology, 100 followed by LMA, we could for the first time (1) confirm and quantify the suggested inverse correlation of the CO and FeC bond strength 37,101 and the special role of CO···H bonding in Mb 102 and (2) could successfully clarify the binding mode of azanone (HNO) to the heme group of Mb, 103 a long debated topic 23,104,105 . Similar as in Mb, the binding of CO to Ngb is a reversible process.…”

“…19,20 Like Hb or Mb, Ngb can coordinate small signaling molecules L such as CO, NO, O 2 , H 2 S, CN À , NO Á via the iron atom of the porphyrin ring. Their key role is to cause conformational changes of the protein resulting in diverse enzymatic activities, [21][22][23] where in higher doses, ligands such as CO or H 2 S can lead to poisoning 24,25 or to oxidative stress. 20 In the absence of an external ligand there are significant structural differences between Hb and Mb on the one hand and Ngb on the other hand.…”

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study

“…Hydrogen sulfide (H 2 S) is a ubiquitous gaseous molecule that is endogenously produced by cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) within the transsulfuration pathway [ 21 – 23 ]. Since it was first identified as a novel gasotransmitter, along with nitric oxide and carbon monoxide, ample evidence has shown the importance of H 2 S in the regulation of multiple physiological functions [ 24 – 26 ]. In bone tissue, H 2 S has been well documented to play a critical role in bone pathologies.…”

Role of Hydrogen Sulfide and Polysulfides in Neurological Diseases: Focus on Protein S-Persulfidation

“…Polysulfides, novel H 2 S-derived molecules, are generated in mammal cells via either enzymatic or non-enzymatic pathways [ 21 ]. Besides, polysulfides could also be formed by the chemical interactions between H 2 S and NO [ 62 - 64 ]. However, this crosstalk between H 2 S and NO might be responsible for the production of polysulfides in mammalian tissues as such a reaction could occur under physiological conditions [ 63 ].…”