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Nitric Oxide (NO) and Cancer pp 459–477Cite as

Nitric Oxide Donors Are a New Class of Anti-cancer Therapeutics for the Reversal of Resistance and Inhibition of Metastasis

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Several novel therapeutic strategies are currently being explored for the treatment of tumors that are refractory to conventional cytotoxic therapies. Further, therapies aimed at the prevention and treatment of metastasis are also being investigated in pre-clinical and clinical studies. Most of these novel therapeutics are aimed at targeting gene products that regulate resistance and metastasis and have yielded several FDA-approved drugs/antibodies for the treatment of specific cancers. Nitric oxide donors, such as nitroglycerine which has been approved for the treatment of cardiovascular diseases, have been examined for their potential role in the treatment of cancer. NO donor-induced anti-tumor activities have been documented in several in vitro and in vivo animal studies. In addition, nitroglycerine therapeutic application in cancer patients has been initiated. Depending on the level of NO released and sustained, it is well documented that high levels of NO are anti-tumorigenic due to their complex activities, such as inhibiting constitutively hyperactivated cell survival/anti-apoptotic pathways and leading to their ability to sensitize drug/immune-resistant tumor cells to apoptosis by cytotoxic drugs. In addition, inhibition of such survival pathways also leads to the regulation of gene products that participate in the epithelial to mesenchymal transition (EMT) and metastasis and result in the inhibition of metastasis. Hence, NO donors can exert simultaneously a multitude of anti-cancer activities, including enhancement of apoptotic stimuli, inhibition of metastasis, inhibition of angiogenesis, and inhibition of hypoxia, depending on the concentration of the NO donor and on the cancer type and stage. Therefore, while novel therapeutics are being tested for specific anti-tumor targeting effects, we suggest that activation of endogenous iNOS or exogenous NO donors can substitute a large number of specific agents and may be considered as universal anti-cancer therapeutics when used alone or in combination with subtoxic cytotoxic drugs. Thus, the development of a new generation of NO donors with minimal toxicity and higher anti-tumor efficacy is warranted for investigation in clinical trials in cancer patients

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Acknowledgments

The author acknowledges the various associates in his laboratory and collaborators for their valuable contributions and whose works were an integral part of this manuscript. The author is also grateful for the assistance of Katherine Wu, Erica Keng, and Tiffany Chin in the preparation of this manuscript. The continuous assistance of the UCLA Jonsson Comprehensive Cancer Center is also acknowledged.

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Authors and Affiliations

  1. Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California at Los Angeles, Le Conte Avenue, Los Angeles, CA, 90095-1747, USA

    Benjamin Bonavida, Stavroula Baritaki & Ali R. Jazirehi

  2. Unidad de Invastigacion en Enfarmeda des Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico

    Sara Huerta-Yepez

  3. Unidad de Investigacion Medica En Inmunologia e Infactologia, Hospital de Infectologia. CMN “LA Caza” IMSS, Mexico City, Mexico

    Mario I. Vega

  4. Hematology/Oncology, Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, USA

    James Berenson

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  1. Benjamin Bonavida
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  2. Stavroula Baritaki
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  3. Sara Huerta-Yepez
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  4. Mario I. Vega
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  5. Ali R. Jazirehi
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  6. James Berenson
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Corresponding author

Correspondence to Benjamin Bonavida .

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Editors and Affiliations

  1. Dept. Microbiology, Immunology &, Molecular Genetics, University of California, Los Angeles, Charles E. Young Dr. E. 609, Los Angeles, 90095, California, USA

    Benjamin Bonavida

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Bonavida, B., Baritaki, S., Huerta-Yepez, S., Vega, M.I., Jazirehi, A.R., Berenson, J. (2010). Nitric Oxide Donors Are a New Class of Anti-cancer Therapeutics for the Reversal of Resistance and Inhibition of Metastasis. In: Bonavida, B. (eds) Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1432-3_24

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  • DOI: https://doi.org/10.1007/978-1-4419-1432-3_24

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  • Online ISBN: 978-1-4419-1432-3

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