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* and Jianbo Xiao* Pages 1561 - 1595 ( 35 )
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.
Nitric oxide, Cancer, nNOS, iNOS, eNOS, immunity, pleiotropic signaling.
Clinical Research Center, Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Student Research Committee, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Department of Orthopedic Surgery, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Purdue Quantum Science and Engineering Institute, Purdue University, West Lafayette, IN 47907, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Department of Biochemistry, Purdue University, West Lafayette, IN 47907, Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense