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Erschienen in: Breast Cancer 2/2014

01.03.2014 | Original Article

Apogossypolone induces autophagy and apoptosis in breast cancer MCF-7 cells in vitro and in vivo

verfasst von: Xiaoge Niu, Shaobin Li, Fang Wei, Jie Huang, Gang Wu, Liang Xu, Dongsheng Xu, Senming Wang

Erschienen in: Breast Cancer | Ausgabe 2/2014

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Abstract

Objective

Apogossypolone (ApoG2), a new derivative of gossypol, is a potent cell-growth inhibitor. ApoG2 has been demonstrated to have superior anti-tumor activity than gossypol in Bcl-2 transgenic mice. The purpose of this study was to investigate the inhibitory effect of ApoG2 on breast cancer cell line MCF-7 in vitro and in vivo, and to investigate its anti-tumor mechanism.

Methods

MCF-7 cell line in culture was treated with ApoG2. The inhibitory effects of ApoG2 on cell growth were measured by MTT and colony-formation assay. The cell apoptotic rate and cell cycle were analyzed by use of flow cytometry (FCM). The ultrastructural changes were observed by transmission electron microscopy. Autophagy was detected by acridine orange staining. Expression of Bcl-2, Bax, and Beclin 1 proteins was measured by western blot analysis.

Results

The inhibitory effect of ApoG2 on MCF-7 cell proliferation was dose and time-dependent. The maximum effect was observed when cells were incubated for 72 h with 40 μM ApoG2. ApoG2 at 5 μM also inhibited colony formation. FCM assay indicated that ApoG2 induced cell apoptosis and caused cell arrest in the S phase and G2/M phase. Transmission electron microscopic examination and acridine orange staining showed that ApoG2 induced intracellular autolysosome formation. Furthermore, ApoG2 reduced Bcl-2 expression, and enhanced expression of Bax and Beclin 1. Xenografting of MCF-7 cells in mice can also be inhibited by ApoG2.

Conclusion

ApoG2, a novel anti-apoptotic Bcl-2 agent, inhibits proliferation of breast cancer cell line MCF-7 by inducing cell apoptosis and autophagy.
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Metadaten
Titel
Apogossypolone induces autophagy and apoptosis in breast cancer MCF-7 cells in vitro and in vivo
verfasst von
Xiaoge Niu
Shaobin Li
Fang Wei
Jie Huang
Gang Wu
Liang Xu
Dongsheng Xu
Senming Wang
Publikationsdatum
01.03.2014
Verlag
Springer Japan
Erschienen in
Breast Cancer / Ausgabe 2/2014
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-012-0372-z

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