Induction of Apoptosis by an Extract of Persian Gulf Marine Mollusc, Turbo Coronatus through the Production of Reactive Oxygen Species in Mouse Melanoma Cells

OBJECTIVE: A variety of approaches such as surgery, chemotherapy, radiotherapy, hormonal therapy and immunotherapy are used to treat melanomas, but unfortunately in most case, the response is very weak and often side effects are serious. This study concerns selective toxicity of an extract of Turbo coronatus on cells and mitochondria from a syngeneic mouse model of melanoma. METHODS: Cells and mitochondria isolated from extra tumoral and melanoma tissues were exposed toa T. coronatus crude extract and fractions obtained by gel-filtration chromatography and assayed for mitochondrial and cellular parameters. RESULT: Crude extract (375, 750 and 1,500 µg/ml) and fraction 1; F1; (275, 550 and 1100 µg/ml) of T. coronatus extract induced a significant (p<0.05) increase of the reactive oxygen species (ROS) level, swelling of mitochondria, collapse of mitochondrial membrane potential (MMP), release of cytochrome c and caspase-3 activation only in the mitochondria and cells obtained from melanoma but not extra tumoral tissues. In addition, the F1 fraction decreased the percentage of viable cells and induced apoptosis in melanoma cells. CONCLUSION: For the first time we could demonstrate that the F1 fraction of a T. coronatus extract, selectively induces ROS mediated cytotoxicity by directly targeting mitochondria in melanoma tissues and it may be a suitable candidate for novel drug treatment of malignant melanomas.