Comparison Of Cancer Prevention Effect And Mechanism Of The Camellia Sinensis Varieties And The Oxidation Of Catechins

Tea plant(Camellia sinensis L.) is a native species of China and their leaves are processed with different methods into daily consumed teas. Although the research on health benefit of tea attracted plenty of attention, the comparison of the biological effects among the diversity of C. sinensis species and the elucidation of their biochemical mechanisms were still not lunched yet. In the present study, we collected 14 typical C. sinensis varieties in China to investigate their cancer prevention effect and mechanism among multiple in vitro and in vivo models including breast cancer cell lines, obese animals and chemical-induced breast cancer in rats, and searched for an interpretation from the aspect of chemical constituents and biological targets. We found the anti-proliferation effect of C. sinensis varieties differed statistically significant with a positive correlation of ester catechins content, the mechanism refers to the inactivation of mTOR signaling pathway. In addition, the anti-obesity effect of C. sinensis varieties plays positive correlation with anti-proliferation effect in vitro, and shows significant differences with regulation of both body weight and lipid metabolism in plasma. Moreover, adding 5%(w/w) Yunnan resistant#10 tea powder into diet significantly reduced the incidence and multiplicity of MNU induced breast cancer in rats through activation of AMPK and inactivation of mTOR.The different processing methods of tea bring variation of oxidation status of catechins. Green tea is simply post processed in a non-fermentation manner which is considered as conserving the most natural chemical constituents including catechins. While black tea is processed by extended fermentation procedure, most catechins in black tea are present as polymers. In the present study, we used same C. sinensis variety leaves as the material to process into green and black tea with typical methods, focused on the influence of anti-proliferation effect in vitro by the post processing methods of green tea and black tea, which effectively avoid the interference from other factors. Further, native EGCG and chemically oxidized EGCG were introduced to elucidate the mechanism between catechin oxidation and anti-proliferation effect in vitro. The results showed green tea and native EGCG are more potent in inhibition of proliferation of oral cavity cancer cell line Tca8113 in vitro than black tea and oxidized EGCG, respectively. And we also demonstrated the capability of green tea and native EGCG in generating H2O2 in cell culture medium and inhibition of thioredoxin reductase activity are significantly stronger than which of black tea and oxidized EGCG, respectively.Thioredoxin reductase (TrxR) is a molecular target for cancer therapy and the anticancer mechanism of both of cisplatin and EGCG involve TrxR inhibition. In order to reveal the mechanism between TrxR and cancer, another platinum drug nedaplatin (NDP) was employed to investigate the interaction mechanism with TrxR. In mice bearing ascitic hepatoma 22 (H22) cells, TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity and the inhibition of ascitic fluid volume was established (r= 0.978, p<0.01), this result also provided an essential reference for anticancer research of EGCG. As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with 2 to 5-fold more antioxidant enzymes and glutathione-predominant non-protein free thiols. When buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, was co-administered with NDP, this adaptive response was largely eliminated, leading to the decimation of the H22 cell population. In conclusion, the pharmacological effect of NDP involves inhibition of TrxR activity, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH by using NDP and BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR by using NDP alone. This conclusion provides a new supportive theory for the application of EGCG in cancer treatment.