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.
Highlights
Primary liver cancer is one of the most frequent malignant tumors, representing the fifth most common malignancy worldwide and the second leading cause of cancer deaths, with a 5‐year survival rate of 17% (Fujise et al, 2016; Llovet et al, 2012)
CFT‐1 treatment was effective in inhibiting the progression of NDEA‐induced liver cancer, including inhibiting histopathological and ultrastructural changes, reducing the incidence, size, number of hepatic nodules and preventing the hepatic adenoma or hepatocellular carcinoma (HCC) formation
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%)
Summary
Primary liver cancer is one of the most frequent malignant tumors, representing the fifth most common malignancy worldwide and the second leading cause of cancer deaths, with a 5‐year survival rate of 17% (Fujise et al, 2016; Llovet et al, 2012). Epidemiological studies indicated that dietary intake of tea may prevent and reduce the risk of different types of malignancies, including liver cancer (Rady, Mohamed, Rady, Siddiqui, & Mukhtar, 2018) These beneficial effects of green tea are primarily attributed to the presence of a type of polyphenols known as catechins and its monomer, including epigallocatechin‐3‐gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), and catechin. Our previous studies found that EGCG, as well as EC, ECG, and EGC, may bind to some cancer‐ related proteins in TPK‐RAS‐MAPK and NF‐κB signaling pathways when used molecular docking of these bioactive substances (Zheng, Chen, & Lu, 2011) It remains unclear whether these mechanisms contributed to the cancer preventive effects in vivo. In this study, we evaluated the chemopreventive properties of EGCG‐rich tea CFT‐1 on N‐nitrosodiethylamine (NDEA)‐induced HCC and its underlying mechanisms
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