Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways

• DOI: 10.1016/j.biopha.2021.112409
• Publication Date: 2021-11-12T22:09:04Z
• Authors: Nour Y.S. Yassin; Sameh F. AbouZid; Asmaa M. El-Kalaawy; Tarek M. Ali; Mazen M. Almehmadi; Osama M. Ahmed
• Keywords: Silybum marianum; Silibinin; Milk Thistle

Hepatocellular carcinoma (HCC) has been identified as one of the most deadly malignancies with limited therapeutic efficacy worldwide. However, understanding molecular mechanisms crosstalk between signaling pathways in HCC and predicting cancer cell responses to targeted interventions remain be challenge. Thus, this study, we aimed evaluate anticancerous Silybum marianum total extract (STE), silymarin (Sm), silibinin (Sb) against experimentally-induced rats. In vitro investigations were also performed anticancer effects lines (HepG2 Huh7) confirmed. Wistar rats given diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4) orally treated STE (200 mg/kg body weight (bw)), Sm (150 bw), Sb (5 bw) every other day from 1st or 16th week 25th DEN/AAF/CCl4 injection. Treatment STE, Sm, inhibited growth cancerous lesions DEN/AAF/CCl4-treated This inhibition was associated Ki-67 expression repression HGF/cMet, Wnt/β-catenin, PI3K/Akt/mTOR pathways. improved liver function biomarkers tumor markers (AFP, CEA, CA19.9) increased protein albumin levels serum. treatment noted reduce hepatic production lipid peroxides, increase glutathione content, induce activities antioxidant enzymes These results indicate that exert anti-HCC through multiple pathways, including suppression enhancement defense mechanisms.