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Dibenzoylmethane activates Nrf2-dependent detoxification pathway and inhibits benzo(a)pyrene induced DNA adducts in

R K Thimmulappa1, T Rangasamy, J Alam

  • 1Bloomberg School of Public Health, Johns Hopkins University, Department of Environmental Health Sciences, Baltimore, MD 21205-2179, USA.

Medicinal Chemistry (Shariqah (United Arab Emirates))
|September 11, 2008
PubMed

Insights

Dibenzoylmethane (DBM), found in licorice, shows promise in preventing lung cancer. It activates the Nrf2 pathway, enhancing the detoxification of carcinogens like those in cigarette smoke.

Area of Science:

  • Chemoprevention
  • Molecular Biology
  • Toxicology

Background:

  • Lung cancer is primarily caused by cigarette smoke carcinogens.
  • Phytochemicals can inhibit carcinogenesis by boosting carcinogen detoxification.
  • Dibenzoylmethane (DBM), a licorice compound, is structurally similar to curcumin, a known cancer chemopreventive agent.

Purpose of the Study:

  • To investigate the chemopreventive effects of DBM in lung cancer.
  • To identify DBM's molecular targets and mechanism of action.
  • To evaluate DBM's efficacy against benzo[a]pyrene-induced DNA damage in lungs.

Main Methods:

  • Administration of DBM to A/J mice exposed to benzo[a]pyrene.
  • Oligonucleotide microarray analysis to identify gene expression changes in lung tissue.
  • Nrf2-dependent reporter assays and electrophoretic mobility shift assays (EMSA) in mouse hepatoma cells.

Main Results:

  • DBM significantly reduced benzo[a]pyrene-induced DNA adducts in mouse lungs.
  • Microarray analysis revealed DBM upregulates cytoprotective genes, including Nrf2-regulated phase II enzymes.
  • DBM dose-dependently increased antioxidant response element (ARE) activity, confirming Nrf2 activation.
  • EMSA demonstrated that DBM enhances Nrf2 DNA binding activity.

Conclusions:

  • DBM exhibits chemopreventive efficacy in the lungs by inhibiting carcinogen-induced DNA damage.
  • DBM functions by activating the Nrf2 pathway, leading to the induction of phase II detoxification enzymes.
  • DBM enhances the detoxification of benzo[a]pyrene, suggesting its potential as a lung cancer preventive agent.

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