Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis

Inorg Chem. 2016 Sep 19;55(18):9383-92. doi: 10.1021/acs.inorgchem.6b01562. Epub 2016 Aug 30.

Abstract

Nitric oxide (NO) is an important cellular signaling molecule that modulates various physiological activities. Angiogenesis-promoting activities of NO-donor drugs have been explored in both experimental and clinical studies. In this study, a structurally well characterized and water-soluble neutral {Fe(NO)2}(9) DNIC [(S(CH2)2OH)(S(CH2)2NH3)Fe(NO)2] (DNIC 2) was synthesized to serve as a NO-donor species. The antitumor activity of DNIC 2 was determined by MTT assay, confocal imaging, and Annexin-V/PI staining. The IC50 values of DNIC 2 were 18.8, 42.9, and 38.6 μM for PC-3, SKBR-3, and CRL5866 tumor cells, respectively. Moreover, DNIC 2 promoted apoptotic cell death via activation of apoptosis-associated proteins and inhibition of survival associated proteins. In particular, DNIC 2 treatment suppressed PC-3 tumor growth by 2.34- and 19.3-fold at 7 and 21 days, in comparison with the control group. These results indicate that water-soluble DNIC 2 may serve as a promising drug for cancer therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Female
  • Humans
  • Iron / chemistry
  • Iron / pharmacology
  • Iron / therapeutic use*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Donors / therapeutic use*
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / pharmacology
  • Nitrogen Oxides / therapeutic use*
  • Solubility
  • Water / chemistry

Substances

  • Antineoplastic Agents
  • Nitric Oxide Donors
  • Nitrogen Oxides
  • Water
  • dinitrosyl iron complex
  • Iron