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Fractional deletion of Compound Kushen Injection indicates cytokine signaling pathways are critical for its perturbation of the cell cycle

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  • معلومة اضافية
    • بيانات النشر:
      Nature Publishing Group
    • الموضوع:
      2019
    • Collection:
      The University of Adelaide: Digital Library
    • نبذة مختصرة :
      Published online: 02 October 2019 ; We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets. ; T. N . Aung, S. Nourmohammadi, Z. Qu, Y. Harata-Lee, J. Cui, H. Y. Shen, A. J. Yool, T. Pukala, Hong Du, R. D. Kortschak, W. Wei, D. L. Adelson
    • File Description:
      application/pdf
    • ISSN:
      2045-2322
    • Relation:
      Scientific Reports, 2019; 9(1):14200-1-14200-16; http://hdl.handle.net/2440/128505; Aung, T.N. [0000-0003-4150-0426]; Nourmohammadi, S. [0000-0002-9469-2874]; Yool, A.J. [0000-0003-1283-585X]; Pukala, T. [0000-0001-7391-1436]; Kortschak, R.D. [0000-0001-8295-2301]; Adelson, D.L. [0000-0003-2404-5636]
    • الرقم المعرف:
      10.1038/s41598-019-50271-4
    • الدخول الالكتروني :
      http://hdl.handle.net/2440/128505
      https://doi.org/10.1038/s41598-019-50271-4
    • Rights:
      © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
    • الرقم المعرف:
      edsbas.A49C5B8B