Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating
Kazim Sahin1, Cemal Orhan, Mehmet Tuzcu
1a Department of Animal Nutrition, Faculty of Veterinary Science , Firat University , Elazig , Turkey.
Abstract:
Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.
Insights
Lycopene effectively inhibited diethylnitrosamine (DEN)-induced liver cancer in rats by reducing tumor growth and reversing harmful biochemical changes. This natural compound activates antioxidant pathways and inhibits inflammation and mTOR signaling, offering chemopreventive benefits.
Area of Science:
- Hepatology and Cancer Research
- Nutritional Biochemistry
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with high mortality rates.
- Diethylnitrosamine (DEN) is a known carcinogen used to induce liver cancer in experimental models.
- Lycopene, a potent antioxidant found in tomatoes, has shown potential chemopreventive properties.
Purpose of the Study:
- To investigate the protective mechanisms of lycopene against DEN-induced hepatocarcinogenesis in a rat model.
- To evaluate the impact of lycopene on key biochemical markers and signaling pathways involved in liver cancer development.
Main Methods:
- Hepatocarcinogenesis was induced in rats using DEN and phenobarbital promotion.
- Rats were administered lycopene orally for 4 weeks prior to and during the 24-week experimental period.
- Biochemical analyses included serum enzymes, malondialdehyde (MDA), antioxidant enzymes, and Western blotting for signaling proteins (NF-E-2-related factor-2, heme oxygenase-1, NF-κB, cyclooxygenase-2, mTOR pathway components).
Main Results:
- Lycopene significantly reduced the incidence, number, size, and volume of hepatic nodules.
- Lycopene reversed DEN-induced increases in liver damage markers (ALT, AST, total bilirubin) and MDA, while restoring antioxidant enzyme levels.
- Lycopene upregulated the Nrf2/HO-1 antioxidant pathway and downregulated the inflammatory NF-κB/COX-2 pathway.
- Lycopene inhibited the mTOR signaling pathway, decreasing levels of p-mTOR, p-p70S6K1, p-4E-BP1, and Akt.
Conclusions:
- Lycopene demonstrates significant chemopreventive activity against DEN-induced hepatocarcinogenesis in rats.
- Lycopene exerts its protective effects by activating antioxidant signaling, suppressing inflammation, and inhibiting the mTOR pathway.
- These findings highlight lycopene as a promising agent for the prevention of liver cancer.
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