title: In vitro antioxidative potential of lactoferrin and black tea polyphenols and protective effects in vivo on carcinogen activation, DNA damage, proliferation, invasion, and angiogenesis during experimental oral carcinogenesis.
abstract: The present study was designed to evaluate the in vitro antioxidant potential of bovine lactoferrin (bLF) and black tea polyphenols [Polyphenon-B (P-B)] as well as in vivo inhibitory effects on the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinomas. Antioxidant activity was screened using a panel of assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), hydroxyl radical anion (OH*), superoxide anion (O2*-), and nitric oxide (NO) radical scavenging assays as well as assay for reducing power. The chemopreventive potential of bLF and P-B was assessed in the HBP model based on the modulatory effects on DMBA-induced oxidative DNA damage as well as the expression of proteins associated with carcinogen activation (CYP1A1, CYP1B1), cell proliferation [cyclin D1, proliferating cell nuclear antigen (PCNA), glutathione S-transferase pi (GST-P)], angiogenesis [vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR1)], and invasion and metastasis [matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of MMP-2 (TIMP-2)]. Both bLF and P-B showed high radical scavenging activity and reductive potential. Although administration of bLF and P-B alone suppressed DMBA-induced HBP tumors, combined administration of bLF and P-B was more effective in inhibiting HBP carcinogenesis by inhibiting oxidative DNA damage, carcinogen activation, cell proliferation, invasion, and angiogenesis. Our study suggests that the antioxidative property of bLF and P-B may be responsible for chemoprevention of HBP carcinogenesis by modulating multiple molecular targets.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
authors.forename: P Vidjaya
authors.initials: PV
authors.lastname: Letchoumy
authors.forename: K V P Chandra
authors.initials: KV
authors.lastname: Mohan
authors.forename: J J
authors.initials: JJ
authors.lastname: Stegeman
authors.forename: H V
authors.initials: HV
authors.lastname: Gelboin
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Nagini
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D019938:Cyclin D1 / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004249:DNA Damage; D016166:Free Radical Scavengers / Q000494:pharmacology; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D016166:Free Radical Scavengers; D010636:Phenols; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; C506663:polyphenon B; D019716:Tissue Inhibitor of Metalloproteinase-2; D019938:Cyclin D1; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D040281:Vascular Endothelial Growth Factor Receptor-1; D007781:Lactoferrin; D020780:Matrix Metalloproteinase 9