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


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.


CONCLUSIONS
Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.
Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India. kalpanachelian@gmail.com
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Kalpana Deepa Priya
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Gayathri
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Gunassekaran
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Murugan
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Sakthisekaran
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity; D001937:Brassica / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D017879:Isothiocyanates; D015227:Lipid Peroxidation / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D001564:Benzo(a)pyrene; D006861:Hydrogen Peroxide; D053148:Caspase 3; C016766:sulforaphane