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.
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.
Murugan
Ramalingam Senthil
RS
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Mohan
Kurapathy Venkata Poorna Chandra
KV
Uchida
Koji
K
Hara
Yukihiko
Y
Prathiba
Duvuru
D
Nagini
Siddavaram
S
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
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