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01.12.2017 | Primary Research | Ausgabe 1/2017 Open Access

Cancer Cell International 1/2017

Induction of apoptosis and proliferation inhibition of hepatocellular carcinoma by 6-chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (BA): in vitro and vivo studies

Zeitschrift:
Cancer Cell International > Ausgabe 1/2017
Autoren:
Yun Huang, Guohua Liu, Feng Yang, Xiaowei Xing, Ying Li, Zhijun Huang, Hong Yuan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12935-017-0435-5) contains supplementary material, which is available to authorized users.
Yun Huang and Guohua Liu contributed equally to this work

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.
Zusatzmaterial
Additional file 1: M1. Structure identification of compounds BA by mass spectrum. BA(C21H17ClN2O) m/z: calculated for [M+H]+: 349.5, found [M+H]+: 349.2.
Additional file 2: M2. Structure identification of compounds BA by Hydrogen spectrum. 1H NMR(500 MHz, TMS): δ 8.40(d, 1H), 7.90(d, 2H), 7.70(d, 1H), 7.65(s, 1H), 7.55(d,2H), 7.45(d,2H), 7.30(d,2H), 5.0(s,3H), 4.30(s,1H), 3.40(s, 2H).
Additional file 3: M3. Structure identification of compounds BA by Carbon spectrum. 13C NMR(125 MHz, TMS): δ 174.14, 167.47, 155.27, 150.52, 140.56, 134.04, 131.96, 128.97, 127.38, 126.50, 124.75, 123.34, 117.29, 115.06, 101.29, 61.79, 55.75, 49.01, 30.48, 29.32, 17.59.
Literatur
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