Hemimycale Arabica Induced Non-Cytotoxic Anti-Migratory Activity in Hepatocellular Carcinoma In Vitro

OBJECTIVE: In this work, we represented new non-cytotoxic treatments to avoid serious side effects of current used cytotoxic anticancer drugs. These treatments can compensate in finding convenient treatment for each individual case using a single agent from marine sponge Hemimycale arabica. METHODS: The ethanol extract was partitioned by cold sequential liquid-liquid extraction to afford petroleum ether, diethyl ether, dichloromethane and ethyl acetate fractions. Chemical composition of H. arabica was performed by gas-liquid chromatography and gas chromatography-mass spectroscopy. Anticancer activity was evaluated by means of cytotoxicity, apoptosis induction, tumor cell migration inhibition and expression analysis of proliferation and migration-related genes. RESULTS: Our results revealed that all treatments were non-cytotoxic except for dichloromethane fraction which exhibited moderate cytotoxic activity. Caspase-independent apoptosis was induced by total ethanol and dichloromethane fractions while ethyl acetate fraction induces caspase-dependent apoptosis. All treatments inhibited matrix metalloproteinase-independent migration. Petroleum ether and dichloromethane inhibited migration through the down-regulation of FGF and it could be used as anticancer therapy for VEGF-resistance patients. While ethanol inhibited tumor cell migration through down-regulation of all tested genes expression. Ether and ethyl acetate fractions exerted anti-migratory activity without affecting the tested genes. All resuls were statistically significant at p˂0.05. CONCLUSION: Total ethanol extract is a promising non-cytotoxic anticancer agent because of its powerful apoptosis induction and capability to block tumor cell migration. Petroleum ether and ether fractions area weak non-cytotoxic anti-migratory agents. Dichloromethane could be a moderate cytotoxic anti-migratory agent induced caspase-independent apoptosis. It could be used in anticancer therapy for VEGF-resistance patients through downregulation of FGF. Ethyl acetate fraction considered a non-cytotoxic agent exerting moderate anti-migratory activity. The new sponge-derived treatments can solve different resistance problems to find a convenient treatment for each individual case using a single agent.