The World Cancer Research Fund International has released 32 anticancer effects (ACEs) that targeted every stage of cancer processes. Thus, we designed two formulas of natural food combination Diet I and Diet II, mainly produced by elite crop varieties rich in ACEs with different mixture ratios, and evaluated their cancer preventive effects on N‐nitrosodiethylamine (NDEA)‐induced hepatocarcinogenesis. After 20 weeks of dietary intervention, Diet I and Diet II reduced incidence, size, and number of hepatic nodules (p < 0.01) and prevented hepatic tumor formation in NDEA‐induced hepatocarcinogenesis rats. Low‐grade hepatic dysplasia incidence was 20% for Diet II and 40% for Diet I, and apparent hepatocellular carcinomas (HCC) rates were both 0, while 90% HCC in control diet treatment group (p < 0.01). Diet I and Diet II ameliorated abnormal liver function enzymes, reduced serum alpha fetal protein, tumor‐specific growth factor, dickkopf‐related protein 1, tumor necrosis factor‐alpha and interleukin‐6 levels, regulated hepatic phase I and II xenobiotic‐metabolizing enzymes, enhanced antioxidant capacity, suppressed NDEA‐initiated oxidative DNA damage, and induced apoptosis coupled to down‐regulation of proinflammatory, invasion, and angiogenesis markers. Daily intake of combination diet produced from ACEs‐rich elite crop varieties can effectively prevent or delay occurrence and development of NDEA‐induced hepatocarcinogenesis in rats.

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.

This study aims to evaluate the preventive effects of anthocyanins extracts (MAEs) from mulberry variety PR-01 against N-nitrosodiethylamine (NDEA)induced hepatocarcinogenesis in rats. It was found that 150 mg•kg −1 MAEs treatment significantly reduced the NDEA-induced hepatic nodules incidence and hepatocellular carcinoma incidence by 58.30% and 41.70% compared to the model group. Meanwhile, MAEs significantly restored the elevated the liver function enzymes, inhibited the tumor necrosis factor alpha and interleukin-6 levels, elevated the serum interleukin-10 and interferon-γ and increased hepatic glutathione-S-transferase and UDP-glucuronosyltransferase 2B1 enzyme activity. Moreover, 150 mg•kg −1 MAEs supplement enhanced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase activities but reduced the malondialdehyde and thiobarbituric acid-reactive substances content by 37.90% and 44.52%. Furthermore, MAEs pretreatment maintained nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1, heme oxygenase-1, and NAD(P)H: quinine oxidoreductase1 stimulation and inhibited the expression of TNF-α, nuclear factor-kappaB (NF-κB), and cyclooxygenase-2 (COX-2), indicating that MAEs exhibit effectively prevention effects against liver cancer via decreased lipid peroxidation, induced Nrf2-mediated antioxidant enzymes and attenuating the inflammatory mediators COX-2 through NF-κB pathway. Thus, MAEs of mulberry variety PR-01 may be used as a good functional dietary supplement against liver cancer.

The Cellulose synthase (CesA) and Cellulose synthase-like (Csl) gene superfamilies encode key enzymes involved in the synthesis of cellulose and hemicellulose, which are major components of plant cell walls, and play important roles in the regulation of fruit ripening. However, genome-wide identification and functional analysis of the CesA and Csl gene families in strawberry remain limited. In this study, eight CesA genes and 25 Csl genes were identified in the genome of diploid woodland strawberry (Fragaria vesca). The protein structures, evolutionary relationships, and cis-acting elements of the promoter for each gene were investigated. Transcriptome analysis and quantitative real-time PCR (qRT-PCR) results showed that the transcript levels of many FveCesA and FveCsl genes were significantly decreased during fruit ripening. Moreover, based on the transcriptome analysis, we found that the expression levels of many FveCesA/Csl genes were changed after nordihydroguaiaretic acid (NDGA) treatment. Transient overexpression of FveCesA4 in immature strawberry fruit increased fruit firmness and reduced fresh fruit weight, thereby delaying ripening. In contrast, transient expression of FveCesA4-RNAi resulted in the opposite phenotypes. These findings provide fundamental information on strawberry CesA and Csl genes and may contribute to the elucidation of the molecular mechanism by which FveCesA/Csl-mediated cell wall synthesis regulates fruit ripening. In addition, these results may be useful in strawberry breeding programs focused on the development of new cultivars with increased fruit shelf-life.

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