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Abstract Background 6-Chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (BA), a novel sponge-derived compound, has been reported to elicit a cytotoxic effect by inhibiting cell proliferation. Methods In this study, we investigated the anti-tumor effect of BA in human hepatocellular carcinoma (HCC) in vitro and in vivo using SMMC-7721 cells. The impact of BA on SMMC-7721 cells was determined by proliferation (clonogenicity and MTT), apoptosis (flow cytometry with annexin V-FITC labeling) and tumor cell migration (Transwell). Apoptosis-related molecules in the PI3K/AKT signaling pathway were examined via Western blotting. We also evaluated the effects of BA on tumor growth using a xenograft nude mouse model. Results The data showed that BA induced dose-dependent cytotoxicity, anti-proliferation, anti-migration and apoptosis in SMMC-7721 cells, accompanied by activation of caspase-3 and a decreased level of caspase-9. Moreover, BA decreased PI3K and p-AKT levels, which indicated the cytotoxicity of BA through the PI3K/Akt pathway. Finally, we confirmed that BA inhibited tumor growth in an HCC xenograft mouse model. Conclusions We concluded that BA induced apoptosis and decreased PI3K and p-AKT expression in human HCC with no effect on the liver, kidney, spleen or lungs. These findings suggest that BA could provide a novel strategy for the treatment of HCC.