Selective Toxicity of Non-polar Bioactive Compounds of Sea Cucumber (Holothuria sabra) Extracts on Isolated Mitochondria and Hepatocytes of Induced Hepatocellular Carcinoma Rat Model

objective: Hepatocellular carcinoma (HCC) is the fifth most malignant of liver cancer globally. Anti-inflammatory and anti-cancer properties, scientists have begun to further investigate the natural bioactive compounds found in marine animals. Holothuria sabra (H. sabra), a sea cucumber is known to show the mentioned properties. Method: This study examined the selective toxicity of different dilutions of polar and non-polar extracts (n-hexane, diethyl ether, methanolic and aqueous) obtained from H. sabra, on hepatocytes and isolated mitochondria obtained from hepatocellular carcinoma induced rats. In order to induce HCC in rats, diethylnitrosamine (DEN) was injected followed by 2-acetylaminofluorene (2-AAF). Finally, hepatocytes and mitochondria isolated from cancerous and normal hepatocytes were applied for subsequent investigations. Results: Our results show that different concentrations (250, 500 and 1000µg/ml) of the n-hexane, diethyl ether and methanolic extracts significantly (p 0.05) induces reactive oxygen species (ROS) formation and mitochondrial swelling, decreased mitochondrial membrane potential (MMP) disruption, increased cytochrome c release and induced the cell apoptosis phenotypes only in HCC hepatocytes and mitochondria in a time and concentration-dependent manner. Conclusion: Our results suggest that bioactive compounds found in H. sabra can potentially serve as anti-HCC molecules if further studies such as molecular identification, confirmatory in vivo experiments and clinical trials receive satisfactory results.