Murugan Ramalingam Senthil, Mohan Kurapathy Venkata Poorna Chandra, Uchida Koji, Hara Yukihiko, Prathiba Duvuru, Nagini Siddavaram
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
J Gastroenterol. 2007 May;42(5):352-61. doi: 10.1007/s00535-007-2018-z. Epub 2007 May 25.
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.
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.
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.
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.
膳食成分的化学预防已成为控制胃癌发病率的一种新方法。因此，我们评估了红茶多酚（Polyphenon-B）在N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的胃癌发生过程中对氧化还原状态、细胞增殖、凋亡和血管生成的化学预防作用。
将雄性Wistar大鼠分为四组。第1组和第2组大鼠每隔2周经胃内插管给予MNNG（150mg/kg体重），共三次，随后观察26周。第2组大鼠还接受含0.05%Polyphenon-B的基础饮食。第3组动物单独给予0.05%Polyphenon-B。第4组动物作为对照。脂质过氧化和抗氧化剂状态以及脂质过氧化标志物4-羟基壬烯醛（4-HNE）、增殖细胞核抗原（PCNA）、谷胱甘肽-S-转移酶（GST）-pi、Bcl-2、Bax、细胞色素C、半胱天冬酶3、细胞角蛋白和血管内皮生长因子（VEGF）的表达用作生物标志物。
胃内给予MNNG诱导了高分化鳞状细胞癌，表现为脂质和蛋白质氧化减少以及抗氧化状态增加。这与细胞增殖、血管生成和侵袭潜能增加以及凋亡逃避有关，表现为PCNA、GST-pi、Bcl-2、细胞角蛋白和VEGF上调以及Bax、细胞色素C和半胱天冬酶3蛋白表达下调。膳食给予Polyphenon-B有效抑制了MNNG诱导的胃癌发生，这通过氧化还原状态的调节、细胞增殖和浸润的抑制以及与凋亡诱导相关的血管生成得以证明。
本研究提供了证据表明Polyphenon-B对MNNG诱导的胃癌发生具有多功能抑制作用，并表明它可被开发为一种潜在的化学预防剂。
