Abstract
Background6-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.MethodsIn 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.ResultsThe 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.ConclusionsWe 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.
Highlights
Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
We concluded that Background: 6-Chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (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
Summary
Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Chemotherapeutic drugs targeting HCC such as doxorubicin, gemcitabine, oxaliplatin, cisplatin and 5-fluorouracil are a common treatment for systemic therapy. Huang et al Cancer Cell Int (2017) 17:66. These treatments have not demonstrated satisfactory results. Doxorubicin has been routinely used as the sole drug for unresectable HCC, with a response rate of 20% and a median survival time of 4 months [5]. The development of the targeted drug sorafenib, a multi-tyrosine kinase inhibitor, has improved survival rates and has been recommended to treat advanced stage (C) HCC [7]. It is urgent to find new targets and possible molecular pathways for HCC treatment
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