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25-methoxyl-dammarane-3β, 12β, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression

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Tumor Biology

Abstract

While the incidence of cancer continues to increase, the current therapeutic options remain imperfect. Therefore, there is an urgent need to discover new targeted anti-cancer therapies. Testes-specific protease 50 (TSP50) is abnormally expressed in most cancer tissues and downregulation of TSP50 expression can reduce cell proliferation and induce cell apoptosis, which makes it a potential target for cancer therapy. In this study, we constructed a firefly luciferase reporter pGL3-TSP50-3′-UTR as a drug screening model to screen potential candidate compounds that target TSP50 mRNA. We identified the compound 7P3A, which consists of 70 % 25-methoxyl-dammarane-3β, 12β, 20-triol and 30 % artemisinin, as being capable of inhibiting the TSP50-3′-UTR reporter activity, as well as the expression of TSP50. Further investigation revealed that 7P3A could inhibit MDA-MB-231 cell proliferation and induce cell cycle arrest, and over-expression of TSP50 partially reversed the effect of 7P3A. In vivo investigation showed that 7P3A could inhibit tumor growth in a xenograft model of breast cancer. These results suggest that 7P3A exhibits anti-cancer effects, in part, through downregulation of TSP50 expression.

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Acknowledgments

We thank Yan Li and Qiuyue Gu for their assistance in this study. This work was supported by the grants from The National Natural Science Foundation of China (Grant Nos. 81272919, 81272242 and 81502284).

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Authors and Affiliations

  1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China

    Danfeng Wang, Yimeng Wang, Hongshuang Qin & Yongli Bao

  2. Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China

    Danfeng Wang, Yimeng Wang, Yan Rong, Zhenbo Song, Chunlei Yu, Luguo Sun & Yuxin Li

  3. Food Science Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Yuqing Zhao

  4. Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China

    Yuxin Li

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  1. Danfeng Wang
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Correspondence to Yongli Bao or Yuxin Li.

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This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The Chinese Academy of Sciences Animal Care and Use Committee gave approval for the animal experiments. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution. This article does not contain any studies with human participants performed by any of the authors.

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Wang, D., Zhao, Y., Wang, Y. et al. 25-methoxyl-dammarane-3β, 12β, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression. Tumor Biol. 37, 11805–11813 (2016). https://doi.org/10.1007/s13277-016-5037-7

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  • DOI: https://doi.org/10.1007/s13277-016-5037-7

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