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.
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.
Letchoumy
P Vidjaya
PV
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
Mohan
K V P Chandra
KV
Stegeman
J J
JJ
Gelboin
H V
HV
Hara
Y
Y
Nagini
S
S
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
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