title: Role of 5-lipoxygenase in resveratrol mediated suppression of 7,12-dimethylbenz(α)anthracene-induced mammary carcinogenesis in rats.
abstract: Substantial evidences suggest that lipoxygenase-catalyzed products have a strong influence on the development and progression of human cancers. The dietary phytochemical resveratrol has become a focus of intense research owing to its roles in cancer prevention. A single tail vein injection of 7,12-dimethylbenz(a)anthracene (DMBA) was given at a dose of 0.5mg/0.2 ml oil emulsion/100g body weight at 50 days of age of female Sprague-Dawley rats. Rats were treated with resveratrol from 2 weeks before DMBA injection (5 weeks of animal age) and continued to 24 weeks of the experimentation at a dose of 100 μg/rat in the diet. We observed that resveratrol acts as a potent 5-lipoxygenase (5-LOX) inhibitor obtained from natural sources. Our result indicated that resveratrol is a strong antioxidant in reducing lipid peroxidation and preventing DNA damage. It significantly decreased the extent of DNA strand break, inhibited abnormal cell proliferation as evidenced by BrdU labeling index and also induced apoptosis in carcinogen-challenged rat mammary tissue. Increased TGF-β1 expression in resveratrol treated rats is thought to be one of the factors inducing apoptosis to suppress DMBA-induced mammary carcinogenesis.
authors.affiliation: Chemical Carcinogenesis and Chemoprevention Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India. mcbiochem@yahoo.com
authors.forename: Mary
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Das
authors.forename: M
authors.initials: M
authors.lastname: Janarthan
authors.forename: Hari K
authors.initials: HK
authors.lastname: Ramachandran
authors.forename: Malay
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D053960:DNA Breaks / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007975:Leukotriene B4 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D013267:Stilbenes; D053773:Transforming Growth Factor beta1; D019938:Cyclin D1; D007975:Leukotriene B4; D015127:9,10-Dimethyl-1,2-benzanthracene; D001094:Arachidonate 5-Lipoxygenase; D000077185:Resveratrol