Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats.
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. 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.
Wang
Yan
Y
Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.|Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.
Ausman
Lynne M
LM
Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.|Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.
Greenberg
Andrew S
AS
Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.|Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Russell
Robert M
RM
Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.|Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.
Wang
Xiang-Dong
XD
Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.|Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002338:Carotenoids / Q000008:administration & dosage*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D004052:Diethylnitrosamine / Q000633:toxicity; D005234:Fatty Liver / Q000150:complications / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000008:administration & dosage*; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D002273:Carcinogens; D010936:Plant Extracts; D002338:Carotenoids; D004052:Diethylnitrosamine; D000077276:Lycopene