Nitric oxide in cancer metastasis

Cancer Lett. 2014 Oct 10;353(1):1-7. doi: 10.1016/j.canlet.2014.07.014. Epub 2014 Jul 29.

Abstract

Cancer metastasis is the spread and growth of tumor cells from the original neoplasm to further organs. This review analyzes the role of nitric oxide (NO), a signaling molecule, in the regulation of cancer formation, progression, and metastasis. The action of NO on cancer relies on multiple factors including cell type, metastasis stage, and organs involved. Various chemotherapy drugs cause cells to release NO, which in turn induces cytotoxic death of breast, liver, and skin tumors. However, NO has also been clinically connected to a poor cancer prognosis because of its role in angiogenesis and intravasation. This supports the claim that NO can be characterized as both pro-metastatic and anti-metastatic, depending on specific factors. The inhibition of cell proliferation and anti-apoptosis pathways by NO donors has been proposed as a novel therapy to various cancers. Studies suggest that NO-releasing non-steroidal anti-inflammatory drugs act on cancer cells in several ways that may make them ideal for cancer therapy. This review summarizes the biological significance of NO in each step of cancer metastasis, its controversial effects for cancer progression, and its therapeutic potential.

Keywords: Hypoxia; NSAIDs; Signaling; Tumor; iNOS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Cell Hypoxia
  • Disease Progression
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / therapeutic use
  • Prognosis
  • Signal Transduction* / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Nitric Oxide Donors
  • Nitric Oxide