Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth

Antonio Barbieri, Giuseppe Palma, Alessandra Rosati, Aldo Giudice, Antonia Falco, Antonella Petrillo, Mario Petrillo, Sabrina Bimonte, Maria Di Benedetto, Giuseppe Esposito, Paola Stiuso, Alberto Abbruzzese, Michele Caraglia, Claudio Arra

Research output: Contribution to journalArticle

Abstract

Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the β-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS-/- mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth.

Original languageEnglish
Pages (from-to)920-926
Number of pages7
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number4
DOIs
Publication statusPublished - 2012

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Nitric Oxide Synthase Type III
Growth
Neoplasms
Vascular Endothelial Growth Factor A
Angiogenesis Inducing Agents
Adrenal Glands
Inbred C57BL Mouse
Propranolol
Adrenocorticotropic Hormone
Thymus Gland
Melanoma
Nitric Oxide
Proteins
Western Blotting
Immunohistochemistry
Weights and Measures
Cell Line
Enzymes

Keywords

  • B16f10
  • eNOS melanoma
  • NOS isoforms
  • Stress

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. / Barbieri, Antonio; Palma, Giuseppe; Rosati, Alessandra; Giudice, Aldo; Falco, Antonia; Petrillo, Antonella; Petrillo, Mario; Bimonte, Sabrina; Di Benedetto, Maria; Esposito, Giuseppe; Stiuso, Paola; Abbruzzese, Alberto; Caraglia, Michele; Arra, Claudio.

In: Journal of Cellular and Molecular Medicine, Vol. 16, No. 4, 2012, p. 920-926.

Research output: Contribution to journalArticle

Barbieri, A, Palma, G, Rosati, A, Giudice, A, Falco, A, Petrillo, A, Petrillo, M, Bimonte, S, Di Benedetto, M, Esposito, G, Stiuso, P, Abbruzzese, A, Caraglia, M & Arra, C 2012, 'Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth', Journal of Cellular and Molecular Medicine, vol. 16, no. 4, pp. 920-926. https://doi.org/10.1111/j.1582-4934.2011.01375.x
Barbieri, Antonio ; Palma, Giuseppe ; Rosati, Alessandra ; Giudice, Aldo ; Falco, Antonia ; Petrillo, Antonella ; Petrillo, Mario ; Bimonte, Sabrina ; Di Benedetto, Maria ; Esposito, Giuseppe ; Stiuso, Paola ; Abbruzzese, Alberto ; Caraglia, Michele ; Arra, Claudio. / Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. In: Journal of Cellular and Molecular Medicine. 2012 ; Vol. 16, No. 4. pp. 920-926.
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