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

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 (9μmol/mouse/day) against B(a)P (100mg/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. © 2013 Informa Healthcare USA, Inc.