Nitric oxide in cancer metastasis

• This review summarizes the dichotomous effects of NO in tumor metastasis.
• Biological factors influence the pro- and anti-metastatic impact of NO.
• NO induces cytotoxicity and apoptosis to hinder cancer cell growth.
• NO promotes intravasation and angiogenesis to enhance cancer cell growth.
• The bimodal nature of NO facilitates the anti-cancer potential of NO-NSAIDs.

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.