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Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection

BACKGROUND: In this report we examine candidate pathways perturbed by Compound Kushen Injection (CKI), a Traditional Chinese Medicine (TCM) that we have previously shown to alter the gene expression patterns of multiple pathways and induce apoptosis in cancer cells. METHODS: We have measured protein...

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Autores principales: Cui, Jian, Qu, Zhipeng, Harata-Lee, Yuka, Nwe Aung, Thazin, Shen, Hanyuan, Wang, Wei, Adelson, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345000/
https://www.ncbi.nlm.nih.gov/pubmed/30678652
http://dx.doi.org/10.1186/s12885-018-5230-8
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author Cui, Jian
Qu, Zhipeng
Harata-Lee, Yuka
Nwe Aung, Thazin
Shen, Hanyuan
Wang, Wei
Adelson, David L.
author_facet Cui, Jian
Qu, Zhipeng
Harata-Lee, Yuka
Nwe Aung, Thazin
Shen, Hanyuan
Wang, Wei
Adelson, David L.
author_sort Cui, Jian
collection PubMed
description BACKGROUND: In this report we examine candidate pathways perturbed by Compound Kushen Injection (CKI), a Traditional Chinese Medicine (TCM) that we have previously shown to alter the gene expression patterns of multiple pathways and induce apoptosis in cancer cells. METHODS: We have measured protein levels in Hep G2 and MDA-MB-231 cells for genes in the cell cycle pathway, DNA repair pathway and DNA double strand breaks (DSBs) previously shown to have altered expression by CKI. We have also examined energy metabolism by measuring [ADP]/[ATP] ratio (cell energy charge), lactate production and glucose consumption. Our results demonstrate that CKI can suppress protein levels for cell cycle regulatory proteins and DNA repair while increasing the level of DSBs. We also show that energy metabolism is reduced based on reduced glucose consumption and reduced cellular energy charge. RESULTS: Our results validate these pathways as important targets for CKI. We also examined the effect of the major alkaloid component of CKI, oxymatrine and determined that it had no effect on DSBs, a small effect on the cell cycle and increased the cell energy charge. CONCLUSIONS: Our results indicate that CKI likely acts through the effect of multiple compounds on multiple targets where the observed phenotype is the integration of these effects and synergistic interactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5230-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-63450002019-01-29 Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection Cui, Jian Qu, Zhipeng Harata-Lee, Yuka Nwe Aung, Thazin Shen, Hanyuan Wang, Wei Adelson, David L. BMC Cancer Research Article BACKGROUND: In this report we examine candidate pathways perturbed by Compound Kushen Injection (CKI), a Traditional Chinese Medicine (TCM) that we have previously shown to alter the gene expression patterns of multiple pathways and induce apoptosis in cancer cells. METHODS: We have measured protein levels in Hep G2 and MDA-MB-231 cells for genes in the cell cycle pathway, DNA repair pathway and DNA double strand breaks (DSBs) previously shown to have altered expression by CKI. We have also examined energy metabolism by measuring [ADP]/[ATP] ratio (cell energy charge), lactate production and glucose consumption. Our results demonstrate that CKI can suppress protein levels for cell cycle regulatory proteins and DNA repair while increasing the level of DSBs. We also show that energy metabolism is reduced based on reduced glucose consumption and reduced cellular energy charge. RESULTS: Our results validate these pathways as important targets for CKI. We also examined the effect of the major alkaloid component of CKI, oxymatrine and determined that it had no effect on DSBs, a small effect on the cell cycle and increased the cell energy charge. CONCLUSIONS: Our results indicate that CKI likely acts through the effect of multiple compounds on multiple targets where the observed phenotype is the integration of these effects and synergistic interactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5230-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-24 /pmc/articles/PMC6345000/ /pubmed/30678652 http://dx.doi.org/10.1186/s12885-018-5230-8 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Cui, Jian
Qu, Zhipeng
Harata-Lee, Yuka
Nwe Aung, Thazin
Shen, Hanyuan
Wang, Wei
Adelson, David L.
Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title_full Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title_fullStr Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title_full_unstemmed Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title_short Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection
title_sort cell cycle, energy metabolism and dna repair pathways in cancer cells are suppressed by compound kushen injection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345000/
https://www.ncbi.nlm.nih.gov/pubmed/30678652
http://dx.doi.org/10.1186/s12885-018-5230-8
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