Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle

Abstract 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-...

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Autores principales:	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
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Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b912d9a8335549f295a7eb338858c86e
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spelling	oai:doaj.org-article:b912d9a8335549f295a7eb338858c86e2021-12-02T15:09:13ZFractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle10.1038/s41598-019-50271-42045-2322https://doaj.org/article/b912d9a8335549f295a7eb338858c86e2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50271-4https://doaj.org/toc/2045-2322Abstract 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. AungS. NourmohammadiZ. QuY. Harata-LeeJ. CuiH. Y. ShenA. J. YoolT. PukalaHong DuR. D. KortschakW. WeiD. L. AdelsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-16 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	T. N. Aung
title	Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
title_short	Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
title_full	Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
title_fullStr	Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
title_full_unstemmed	Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
title_sort	fractional deletion of compound kushen injection indicates cytokine signaling pathways are critical for its perturbation of the cell cycle
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/b912d9a8335549f295a7eb338858c86e
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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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