title: Modulatory effects of black tea polyphenols on oxidant-antioxidant profile and expression of proliferation, apoptosis, and angiogenesis-associated proteins in the rat forestomach carcinogenesis model.
abstract: BACKGROUND
  Chemoprevention by dietary constituents has emerged as a novel approach to control stomach cancer incidence. We therefore evaluated the chemopreventive effects of black tea polyphenols (Polyphenon-B) on oxidant-antioxidant status, cell proliferation, apoptosis, and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.
  
  
  METHODS
  Male Wistar rats were divided into four groups. Rats in group 1 and 2 were given MNNG (150 mg/kg body weight) by intragastric intubation three times at 2 week intervals and followed for 26 weeks. Rats in group 2 received in addition a basal diet containing 0.05% Polyphenon-B. Group 3 animals were given 0.05% Polyphenon-B alone. Group 4 animals served as controls. The status of lipid peroxidation and antioxidants and the expression of the lipid peroxidation marker 4-hydroxy nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), glutathiones-transferase (GST)-pi, Bcl-2, Bax, cytochrome C, caspase 3, cytokeratins, and vascular endothelial growth factor (VEGF) were used as biomarkers.
  
  
  RESULTS
  Intragastric administration of MNNG induced well-differentiated squamous cell carcinomas that showed diminished lipid and protein oxidation and an increase in antioxidant status. This was associated with increased cell proliferation, angiogenesis, and invasive potential coupled with apoptosis evasion as revealed by upregulation of PCNA, GST-pi, Bcl-2, cytokeratins, and VEGF and downregulation of Bax, cytochrome C, and caspase 3 protein expression. Dietary administration of Polyphenon-B effectively suppressed MNNG-induced gastric carcinogenesis, as evidenced by modulation of oxidant-antioxidant status, inhibition of cell proliferation and infiltration, and angiogenesis associated with apoptosis induction.
  
  
  CONCLUSIONS
  The present study provides evidence that Polyphenon-B exerts multifunctional inhibitory effects on MNNG-induced gastric carcinogenesis and suggests that it can be developed as a potential chemopreventive agent.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors.forename: Ramalingam Senthil
authors.initials: RS
authors.lastname: Murugan
authors.forename: Kurapathy Venkata Poorna Chandra
authors.initials: KV
authors.lastname: Mohan
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Duvuru
authors.initials: D
authors.lastname: Prathiba
authors.forename: Siddavaram
authors.initials: S
authors.lastname: Nagini
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D049109:Cell Proliferation; D018890:Chemoprevention; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D008769:Methylnitronitrosoguanidine; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D016877:Oxidants; D010636:Phenols; D018809:Proliferating Cell Nuclear Antigen; D017392:Thiobarbituric Acid Reactive Substances; C506663:polyphenon B; D008769:Methylnitronitrosoguanidine; C027576:4-hydroxy-2-nonenal