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. 2010 Apr 15;126(8):1788-1796.
doi: 10.1002/ijc.24689.

Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats (V体育平台登录)

Yan Wang  1   2 , Lynne M Ausman  1   2 , Andrew S Greenberg  2   3 , Robert M Russell  1   2 , Xiang-Dong Wang  1   2
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"V体育官网入口" Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats

Yan Wang et al. Int J Cancer. .

Abstract

Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers VSports手机版. We recently showed that high-fat diet (HFD)-induced nonalcoholic steatohepatitis (NASH) promoted diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in a rat model. Using this model, we investigated the efficacy of an equivalent dosage of dietary LY from either a pure compound or a tomato extract (TE) against NASH-promoted hepatocarcinogenesis. Six groups of rats were injected with DEN and then fed either Lieber-DeCarli control diet or HFD with or without LY or TE for 6 weeks. Results showed that both LY and TE supplementations significantly decreased the number of altered hepatic foci expressing the placental form of glutathione S-transferase in the livers of HFD-fed rats. This was associated with significantly lower proliferating cell nuclear antigen positive hepatocytes and cyclinD1 protein, as well as decreased activation of extracellular signal-regulated kinase and nuclear NF-kappaB. Although both LY and TE supplementations reduced HFD-induced lipid peroxidation in the livers, we observed significantly decreased cytochrome P450 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-12) in the HFD+TE fed group but increased nuclear NF-E2-related factor-2 and heme oxygenase-1 proteins in the HFD+LY fed group, relative to HFD feeding alone. These data indicate that LY and TE can inhibit NASH-promoted hepatocarcinogenesis mainly as a result of reduced oxidative stress, which could be fulfilled through different mechanisms. .

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Conflict of interest statement

Conflict of interest statements

Author Disclosures: Yan Wang, Lynne M. Ausman, Andrew S V体育安卓版. Greenberg, Robert M. Russell and Xiang-Dong Wang have no conflicts of interest.

"V体育官网" Figures

FIGURE 1
FIGURE 1
Assessment of Cell proliferation. (A) Hepatocytes expressing PCNA were detected by immunohistochemical assay and then counted from 20 randomly selected fields at ×200 magnification (Insert: typical picture of PCNA positive hepatocytes). (B) Hepatic cyclin D1 protein concentration was measured from whole liver homogenates by using Western blotting. Bars represent means ± SEM, n = 8. * P < 0.05 between groups.
FIGURE 2
FIGURE 2
Hepatic inflammation. (A) The number of inflammatory foci was counted in 20 randomly selected fields at ×200 magnification and expressed as average number per area (cm2) (Insert: typical picture of inflammatory foci with clustering of mainly mononuclear cells). (B) The mRNA expression of multiple proinflammatory cytokines in liver after real-time PCR analysis. Quantification of transcript was relative to the GAPDH mRNA levels. Bars represent means ± SEM, n = 8. * P < 0.05 between groups.
FIGURE 3
FIGURE 3
Oxidative stress and regulatory mechanisms. (A) End products of lipid peroxidation (MDA plus 4-HNE) were measured by using the LPO 586 assay kit; (B–D) Hepatic protein concentrations of CYP2E1, nuclear Nrf2 and HO-1 were measured by using Western blotting. Bars represent means ± SEM, n = 8. * P < 0.05 between groups.
FIGURE 4
FIGURE 4
ERK and NF-κB activation. (A) Both total ERK and phosphorylated ERK in liver were measured by western blotting with use of specific antibodies. The values represent a relative ratio between the phosphorylated form and the total form. (B) The nuclear concentration of active p65 subunit of NF-κB was measured from liver nuclear extracts by using Western blotting. Bars represent means ± SEM, n = 8. * P < 0.05 between groups.
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V体育安卓版 - References

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