Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis

Pharm Biol. 2013 May;51(5):621-8. doi: 10.3109/13880209.2012.761242. Epub 2013 Feb 4.

Abstract

Context: Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties.

Objective: The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 µmol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice.

Materials and methods: Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H2O2) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c.

Results: SFN treatment was found to decrease the H2O2 production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups.

Conclusion: Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / isolation & purification
  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects*
  • Benzo(a)pyrene / toxicity
  • Brassica / chemistry*
  • Caspase 3 / metabolism
  • DNA Fragmentation / drug effects
  • Electrophoresis, Agar Gel
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hydrogen Peroxide / metabolism
  • Isothiocyanates
  • Lipid Peroxidation / drug effects
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Oxidative Stress / drug effects
  • Sulfoxides
  • Thiocyanates / administration & dosage
  • Thiocyanates / isolation & purification
  • Thiocyanates / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • Sulfoxides
  • Thiocyanates
  • Benzo(a)pyrene
  • Hydrogen Peroxide
  • Caspase 3
  • sulforaphane