Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells

M. Marino, P. Galluzzo, S. Leone, F. Acconcia, P. Ascenzi

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO) and 17β-estradiol (E2) are both important in gastrointestinal health and disease. NO contributes to gastrointestinal motility as well as to inflammation and carcinogenic processes. By contrast, E2 reduces the incidence of colon adenoma and carcinoma by about 30%. We report the genomic and non-genomic E2-estrogen receptor (ER) β-induced effects in human colon adenocarcinoma. The effect of NO on ERβ activities was also assessed. The E2-ERβ-dependent gene transcription was inhibited by exogenous NO, whereas some non-genomic E2-dependent effects (e.g. p38/MAP kinase), important for the activation of the apoptotic cascade, were unaffected by NO. However, NO impaired the E2-induced pro-apoptotic cascade in human colon adenocarcinoma cells by inhibiting caspase-3. The effects of NO may reflect chemical modification(s) of Cys residues present in the DNA recognition domain of ERβ as well as in the caspase-3 active site. On the whole, high NO concentrations suppressed the E2 protective effects in the gastrointestinal tract, suggesting that the caspase-dependent apoptotic cascade may become critical under conditions of high redox stress such as occur under specific activation of the immune system by chronic infections or pathogen challenge.

Original languageEnglish
Pages (from-to)559-569
Number of pages11
JournalEndocrine-Related Cancer
Volume13
Issue number2
DOIs
Publication statusPublished - Jun 2006

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells'. Together they form a unique fingerprint.

  • Cite this