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Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells

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Abstract

Cucurbitacin B (Cuc B), a natural compound extracted from cucurbitaceous plants, demonstrated potent anticancer activities, while the underlying mechanisms remain unclear. We investigated the anticancer effect of Cuc B on MCF-7 breast cancer cells. Cuc B drastically decreased cell viability in a concentration-dependent manner. Cuc B treatment caused DNA damage, as shown by long tails in the comet assay and increased γH2AX protein expression. Immunofluorescence staining showed that Cuc B treatment induced nuclear γH2AX foci. Cuc B activated DNA damage pathways by phosphorylation of ATM/ATR [two large phosphatidylinositol-3-kinase-like kinase family (PIKKs) members]. Furthermore, it also induced autophagy, as evidenced by monodansylcadaverine (MDC) staining and autophagic protein expression. In addition, Cuc B treatment led to increased reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-l-cysteine (NAC) pretreatment. NAC pretreatment inhibited Cuc-B-induced DNA damage and autophagy. Taken together, these results suggest that ROS-mediated Cuc-B-induced DNA damage and autophagy in MCF-7 cells, which provides new insights into the anticancer molecular mechanism of Cuc B.

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Acknowledgments

This study was supported by the Science and Technology Development Fund, Macao S.A.R. (FDCT) (No. 039/2014/A1) and the Research Fund of the University of Macau (No. MYRG118(Y2-L4)-ICMS13-CXP).

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The authors declare that there are no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Guowen Ren, Jiajie Guo, Wenxue Li, Jinjian Lu & Xiuping Chen

  2. Department of Obstetrics, Rizhao Hospital of TCM, Rizhao, China

    Tongye Sha

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  1. Guowen Ren
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  2. Tongye Sha
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  3. Jiajie Guo
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Correspondence to Xiuping Chen.

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Ren, G., Sha, T., Guo, J. et al. Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells. J Nat Med 69, 522–530 (2015). https://doi.org/10.1007/s11418-015-0918-4

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  • DOI: https://doi.org/10.1007/s11418-015-0918-4

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