Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model

• Published in: Cancer cell international 2022-11, Vol.22 (1), p.1-333, Article 333
• Main Authors: Hussein, Aya M., El-Beih, Nadia M., Swellam, Menha, El-Hussieny, Enas A.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bax protein; Bcl-2 protein; Bcl-x protein; Biomarkers; Body weight; Cancer therapies; Carcinogenesis; Caspase-3; Diethylnitrosamine; Drug dosages; Experiments; Fruits; Gene expression; HCC; Hepatic antioxidants; Hepatocellular carcinoma; Inflammation; Interleukin 10; Liver cancer; Malignancy; MicroRNAs; miR-21; mRNA; Natural products; NF-κB protein; NF-κB-p65; Oxidative stress; Polyphenols; TNF-α; Tumor necrosis factor-α
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-022-02759-9

Background Hepatocellular carcinoma (HCC) is the most common neoplasm among primary liver malignancies, accounting for 70%–85% of total liver cancer cases worldwide. It is also the second-leading cause of cancer-related death worldwide. Recent research has investigated naturally occurring products high in polyphenolic compounds in the regression and prevention of HCC. This study investigated the chemoprevention effects of pomegranate juice (PJ) and punicalagin (PCG) against diethylnitrosamine (DENA)-induced hepatocarcinogenesis in male albino rats. Methods Animals were randomized into six groups and treated for 11 weeks as follows: group 1 was a negative control group, group 2 was treated orally with 10 mL PJ per kilogram body weight (kg bw), group 3 was treated orally with 18.5 mg PCG/kg bw, and groups 4–6 were injected with an intraperitoneal dose of DENA (50 mg/kg bw) weekly beginning in the third week. Group 4 was a HCC control (DENA-treated group), group 5 was HCC + PJ, and group 6 was HCC + PCG. Results PJ antagonized DENA-induced elevations of ALAT, TNF-α, NF-κB-p65, GST, MDA, and NO and restored total protein, IL-10, SOD, and CAT levels. Moreover, PJ resulted in downregulation of miR-21, Bcl-2, and Bcl-XL and an upregulation of caspase-3 and Bax mRNA expressions. These chemoprevention effects of PJ also alleviated the hepatic preneoplastic lesions induced by DENA. Although PCG treatment induced some modulation in DENA-treated rats, it did not show potent chemoprevention activity and induced some side effects. Conclusion Both of PJ and PCG downregulated miR-21 expression and triggered apoptosis. However, PJ was more effective than pure PCG in alleviating the hepatic antioxidant defense state and the inflammatory status. So, PJ was superior in prevention of DENA-induced hepatocellular carcinogenesis in rats than pure PCG.