Astaxanthin suppresses hepatocellular carcinoma via targeting Wnt/Β-catenin pathway: Experimental study on chemically induced HCC in rats

Abstract Astaxanthin (ATX) is a potent natural antioxidant that shows promise against hepatocellular carcinoma (HCC). We investigated the therapeutic potential of ATX and its impact on Wnt/β-catenin pathway in a rat model, inducing HCC by nitrosodiethylamine (DEN) and carbon tetrachloride (CCl4). Rats were divided into five groups; I: control, II: HCC, III: HCC rats received ATX (5 days/week), IV: HCC rats received doxorubicin (DOX) weekly, V: HCC rats received combination therapy, for 4 weeks. Our results indicate that combination therapy significantly improved serum biomarkers, reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP) levels by 45%, 35%, 49%, respectively compared to untreated HCC rats. Histopathological examination revealed the absence of hepato-carcinogenic nodules in the DOX- and combination-treated groups. Furthermore, combination therapy downregulated Wnt/β-catenin pathway components, decreasing frizzled-7 (FZD-7) by 56%, low-density lipoprotein receptor-related proteins 5/6 (LRP5/6) by 62%, β-catenin by 58%, and upregulating glycogen synthase kinase-3β (GSK3β) by 41% compared to untreated HCC rats. Consequently, the expression of key proteins such as cyclin D1 was ameliorated by 46%. While DOX monotherapy upregulated multidrug resistance protein-1 (MDR1) by 65%, combination therapy mitigated this increase by 36%. These findings highlight that ATX has potential therapeutic benefits in HCC treatment in rats.