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Updated: Jul 17, 2026
The Influence of Liver Resection on Intrahepatic Tumor Growth
Published on: April 9, 2016
An antioxidant effect by acyclic retinoid suppresses liver tumor in mice
Tomohiko Sakabe1, Hiroyuki Tsuchiya, Michiko Endo
1Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago 683-8504, Japan.
Abstract:
The mechanisms of prevention of the development of liver cancer by NIK-333, an acyclic retinoid (ACR), were investigated. The transgenic mice expressing the dominant negative form of retinoic acid receptor alpha (RARE mice), that produce reactive oxygen species and lead to development of liver tumor were used. The effect of NIK-333 on hepatocarcinogenesis in RARE mice was studied. The RARE mice were examined after feeding 0.03% and 0.06% NIK-333 diets at 12 months of age. In the mice fed 0.06% NIK-333 diet, tumor incidence was greatly suppressed, compared to that of wild type mice (0/9 versus 5/9, P<0.05), but not in the mice fed 0.03% NIK-333 diet. In addition, expression of cytochrome p450 4a14 and acyl-CoA oxidase was normalized, and the percentages of positive cells for 8-hydroxy-2'-deoxyguanosine, 4-hydroxy-2-nonenal and proliferating cell nuclear antigen were decreased. Furthermore, expression of beta-catenin and cyclin D1 was also depressed. These data suggest that NIK-333 suppressed liver tumor in association with repression of oxidative stress.
Insights
Acyclic retinoid NIK-333 significantly suppressed liver cancer development in mice by reducing oxidative stress and key cancer-promoting molecules. This suggests NIK-333
Area of Science:
- Hepatology
- Oncology
- Molecular Biology
Background:
- Liver cancer is a major global health concern.
- Oxidative stress plays a critical role in hepatocarcinogenesis.
- Acyclic retinoids (ACRs) show potential in cancer prevention.
Purpose of the Study:
- To investigate the preventive mechanisms of NIK-333, an ACR, against liver cancer.
- To evaluate the efficacy of NIK-333 in a mouse model of liver tumor development.
Main Methods:
- Utilized transgenic RARE mice prone to liver tumors due to oxidative stress.
- Administered diets containing 0.03% and 0.06% NIK-333 to RARE mice at 12 months of age.
- Assessed tumor incidence, gene/protein expression (cytochrome p450 4a14, acyl-CoA oxidase, beta-catenin, cyclin D1), and oxidative stress markers (8-hydroxy-2'-deoxyguanosine, 4-hydroxy-2-nonenal).
Main Results:
- The 0.06% NIK-333 diet significantly suppressed liver tumor incidence (0/9) compared to controls (5/9, P<0.05).
- NIK-333 normalized expression of cytochrome p450 4a14 and acyl-CoA oxidase.
- Reduced markers of oxidative stress and cell proliferation, along with depressed beta-catenin and cyclin D1 expression.
Conclusions:
- NIK-333 demonstrates significant potential in preventing liver cancer development.
- The mechanism involves the repression of oxidative stress pathways.
- NIK-333 may represent a novel therapeutic strategy for liver cancer prevention.
