Chemoprevention of elite tea variety CFT-1 rich in EGCG against chemically induced liver cancer in rats

Abstract

Camellia sinensis (L.) O. Kuntze cv. CFT-1 is an elite tea variety bred by sexual hybridization with a high content of epigallocatechin-3-gallate (EGCG) as 134.2 mg/g (which is 2.54-fold that of the common variety). This study was to evaluate the chemopreventive effects of CFT-1 green tea infusion (CFT-1) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats and its mechanisms. The results showed that CFT-1 had a superior inhibitory effect in NDEA-initiated hepatocarcinogenesis compared to that of common tea. CFT-1 significantly reduced the hepatic nodules incidence, size, and number and prevented the hepatic adenoma or hepatocellular carcinoma (HCC) formation. In particular, CFT-1-treated animals had the least incidence of HCC (8.33%) followed by common tea treatment (40.00%) and model control rats (87.50%). CFT-1 treatment significantly ameliorated abnormal liver function enzymes, reduced serum AFP, CEA, TSGF, and TNF-α levels, inhibited the dickkopf-related protein-1 expression, enhanced antioxidant capacity, suppressed the production of livers 8-hydroxy-2′-deoxyguanosine, and regulated hepatic phase I and II xenobiotic-metabolizing enzymes. Transcriptomic analysis of liver tissue suggested that compared to common tea, administration of CFT-1 regulated larger gene sets, which were located in several important pathways of antioxidants, inflammatory network, xenobiotic-metabolizing enzymes, apoptosis, cell proliferation, and metabolism associated with liver tumorigenesis. We identified some genes as potential molecular targets involved in the prevention of CFT-1 and found that CFT-1 inhibited inflammation response, proliferation, and accelerated apoptosis by inhibiting NF-κB and PI3K/Akt pathway. Thus, EGCG-rich CFT-1 green tea might be a potential choice for liver cancer prevention/treatment in the future.