ABSTRACT
Background: Malignant melanoma is a highly aggressive malignant melanocytic neoplasmwhich resists against the most conventional therapies. Sea cucumber as one ofmarine organisms contains bioactive compounds such as polysaccharide, terpenoidand other metabolites which have anti-cancer, anti-tumor, anti-inflammatory andantioxidant properties. The present study was designed to investigate the anticancerpotential of saponin extracted from sea cucumber Holothuria leucospilata alone andin combination with dacarbazine on B16F10 melanoma cell line
Methods: The B16F10 cell line was treated with different concentrations of saponin [0,4, 8, 12, 16, 20micro g/ml], dacarbazine [0, 1200, 1400, 1600, 1800, 2000micro g/ml] and coadministrationof saponin-dacarbazine [1200 da +8 sp, 1200 da +4 sp] for 24 and 48 hrand the cytotoxic effect was examined by MTT, DAPI, acridine orange/propodium iodide,flow cytometry and caspase colorimetric assay
Results: The results exhibited that sea cucumber saponin, dacarbazine, and coadministrationof saponin-dacarbazine inhibited the proliferation of melanoma cellsin a dose and time dependent manner with IC[50]values of 10, 1400 and 4 +1200micro g/ml,respectively. Morphological observation of DAPI and acridine orange/propodium iodidestaining documented typical characteristics of apoptotic cell death. Flowcytometry assay indicated accumulation of IC[50]treated cells in sub-G1 peak. Additionally,saponin extracted induced intrinsic apoptosis via up-regulation of caspase-3and caspase-9
Conclusion: These results revealed that the saponin extracted from sea cucumber as anatural anti-cancer compound may be a new treatment modality for metastaticmelanoma and the application of sea cucumber saponin in combination withdacarbazine demonstrated the strongest anti-cancer activity as compared with thedrug alone
ABSTRACT
Cancer is the second important reason of mortality in the world. In this regard melanoma was accounted as the most aggressive type of cutaneous cancer. Among drug extracted from natural products from marine organisms have been focused investigations related to chemotherapeutic agents derived from echinoderms such as sea cucumbers and starfish. In the present study, cytotoxic and apoptosis inducing potential of Persian Gulf brittle stars dichloromethane extract were evaluated against melanoma cancers. In this study, anti-proliferative effect of brittle stars dichloromethane extract on B16F10 melanoma cells examined by MTT assay and morphological characterization and death inducing effect of Annexin-PI and PI flow cytometry. The data analysis was performed by SPSS software and p<0.05 were considered significant. The dichloromethane extract of brittle star revealed significant cytotoxic effect on B16F10 melanoma cells with IC[50]= 31 microg/ml which is stronger than inhibitory effect of methanol extract on melanoma cell growth. In addition, brittle star dichloromethane extract recruited apoptotic pathway in the response of 31 microg/ml treatment. This study showed that certain concentrations of dichloromethane brittle stars possess cytotoxic activity that can be used as an anticancer agent used in clinical trial due to cell growth inhibition and apoptosis induction which offer therapeutic investigations of dichloromethane brittle star extract as complementary for melanoma treatment and prevention