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

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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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Acknowledgments

The authors acknowledge Professor Yanfang Zheng (Department of Oncology, the Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital, Guangzhou, People’s Republic of China, 510282) for modifying this manuscript. The authors also acknowledge Dr Fengrong Shi’s contribution to the article (Department of Oncology, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital, Guangzhou, People’s Republic of China, 510282).

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Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital, Guangzhou, 510282, People’s Republic of China

    Xiaoge Niu, Fang Wei, Jie Huang, Gang Wu & Senming Wang

  2. Department of Thoracic Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital, Guangzhou, 510282, People’s Republic of China

    Shaobin Li

  3. Departments of Urology and Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical School, Kansas, USA

    Liang Xu

  4. CBLPATH, 760 Westchester Ave, Rye Brook, NY, 10573, USA

    Dongsheng Xu

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  1. Xiaoge Niu
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  2. Shaobin Li
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  3. Fang Wei
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  4. Jie Huang
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  5. Gang Wu
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  6. Liang Xu
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  7. Dongsheng Xu
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  8. Senming Wang
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Correspondence to Senming Wang.

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Cite this article

Niu, X., Li, S., Wei, F. et al. Apogossypolone induces autophagy and apoptosis in breast cancer MCF-7 cells in vitro and in vivo. Breast Cancer 21, 223–230 (2014). https://doi.org/10.1007/s12282-012-0372-z

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  • DOI: https://doi.org/10.1007/s12282-012-0372-z

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