Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies

Adeleh Sahebnasagh, Fatemeh Saghafi, Sina Negintaji, Tingyan Hu, Mojtaba Shabani-Borujeni, Mohammadreza Safdari, Hassan Rezai Ghaleno, Lingchao Miao, Yaping Qi, Mingfu Wang, Pan Liao, Antoni Sureda, Jesus Simal-Gándara, Seyed Mohammad Nabavi*, Jianbo Xiao*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “doubleedged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

Original languageEnglish
Pages (from-to)1561-1595
Number of pages35
JournalCurrent Medicinal Chemistry
Issue number9
Early online date7 Jul 2021
Publication statusPublished - 1 Mar 2022

Scopus Subject Areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

User-Defined Keywords

  • Cancer
  • eNOS
  • immunity
  • iNOS
  • Nitric oxide
  • nNOS
  • pleiotropic signaling


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