The Anticancer Effect of Rhubarb Officinale Fraction and Sorafenib Against Chemically Induced Hepatocellular Carcinoma in Rats

Abstract

Background: Hepatocellular carcinoma (HCC), the major primary malignant tumour of the liver, represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. Objectives: The aim of this study was to investigate the potential anticancer properties of four Anthraquinones (Aloe-emodin, Emodin, Chysophanol, and Physcion) isolated from the rhizome of Rhubarb and compare between the effect of sorafenib and Rhubarb Officinale fraction on DEN and carbon tetrachloride (CCl4) -   induced hepatocellular carcinoma in rats. Material and methods: The rats were divided into 5 groups (n=12/group normal control, diethylnitrosamine DEN+ carbon tetrachloride CCL4, HCC rats +ANTH(Anthraquinones), HCC rats +SOR(Sorafenib) and HCC rats +mix of ANTH+SOR. Results: Rats in HCC group showed most deteriorated effect in form of increased mortality, liver cancer marker (lipid peroxidation biomarker MDA, inflammation –related genes (TNFa, ILIB, NFKB, TGFB1) and metastasis-related genes (MMP9). Liver tissues of HCC group also exhibited lower level of TIMPI and antioxidant activity (catalase (CAT). All these deleterious effects induced by DEN were reversed after administration of ANTH and SOR with best improvement for the combined group (ANTH+SOR). Conclusions: These findings reveal a better therapeutic effect for ANTH when given with SOR and we attribute this beneficial effect, at least in part, to triggering antioxidant activity, inflammation and metastasis in HCC. Therefore, combined treatment with ANTH and SOR is recommended to enhance the therapeutic potential against HCC.