Estrogen promotes benzo[a]pyrene-induced lung carcinogenesis through oxidative stress damage and cytochrome c-mediated caspase-3 activation pathways in female mice

Cancer Lett. 2011 Sep 1;308(1):14-22. doi: 10.1016/j.canlet.2011.04.007. Epub 2011 May 23.

Abstract

Estrogen may contribute to the development of smoking-induced lung cancer in women. To test this hypothesis, an mouse model was used to investigate the effects of 17 beta-estradiol (E2) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis. We found that B[a]P could cause oxidative stress damage, upregulate mitochondrial cytochrome-c and caspase-3 expression, induce lung carcinogenesis in female mice, E2 promoted these effects of B[a]P while tamoxifen (TAM) inhibited this effects of E2. We conclude that E2 can promote the tumorigenic effects of B[a]P in female mice, and oxidative stress damage and activation of cytochrome-c-mediated caspase-3 pathway may be involved in this process.

MeSH terms

  • Animals
  • Benzo(a)pyrene / pharmacology*
  • Caspase 3 / metabolism*
  • Cytochromes c / metabolism*
  • DNA Damage
  • Disease Models, Animal
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Estradiol / pharmacology*
  • Female
  • Humans
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Random Allocation

Substances

  • Benzo(a)pyrene
  • Estradiol
  • Cytochromes c
  • Caspase 3