Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines

Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines

Traditional Chinese Medicines are promising sources of new agents for controlling cancer metastasis. Compound Kushen Injection (CKI), prepared from medicinal plants Sophora flavescens and Heterosmilax chinensis, disrupts cell cycle and induces apoptosis in breast cancer; however, effects on migratio...

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Main Authors: Saeed Nourmohammadi, Thazin Nwe Aung, Jian Cui, Jinxin V. Pei, Michael Lucio De Ieso, Yuka Harata-Lee, Zhipeng Qu, David L. Adelson, Andrea J. Yool
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Oncology
Subjects:
traditional chinese medicine (TCM)
compound kushen injection (CKI)
cell migration
invasion
cancer
gene regulatory networks
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.00314/full
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spelling doaj-67de71472e354ecca63533fff8659feb2020-11-25T01:01:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-04-01910.3389/fonc.2019.00314453277Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell LinesSaeed Nourmohammadi0Thazin Nwe Aung1Jian Cui2Jinxin V. Pei3Michael Lucio De Ieso4Yuka Harata-Lee5Zhipeng Qu6David L. Adelson7Andrea J. Yool8Adelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaAdelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaAdelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaAdelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaTraditional Chinese Medicines are promising sources of new agents for controlling cancer metastasis. Compound Kushen Injection (CKI), prepared from medicinal plants Sophora flavescens and Heterosmilax chinensis, disrupts cell cycle and induces apoptosis in breast cancer; however, effects on migration and invasion remained unknown. CKI, fractionated mixtures, and isolated components were tested in migration assays with colon (HT-29, SW-480, DLD-1), brain (U87-MG, U251-MG), and breast (MDA-MB-231) cancer cell lines. Human embryonic kidney (HEK-293) and human foreskin fibroblast (HFF) served as non-cancerous controls. Wound closure, transwell invasion, and live cell imaging showed CKI reduced motility in all eight lines. Fractionation and reconstitution of CKI demonstrated combinations of compounds were required for activity. Live cell imaging confirmed CKI strongly reduced migration of HT-29 and MDA-MB-231 cells, moderately slowed brain cancer cells, and had a small effect on HEK-293. CKI uniformly blocked invasiveness through extracellular matrix. Apoptosis was increased by CKI in breast cancer but not in non-cancerous lines. Cell viability was unaffected by CKI in all cell lines. Transcriptomic analyses of MDA-MB-231indicated down-regulation of actin cytoskeletal and focal adhesion genes with CKI treatment, consistent with observed impairment of cell migration. The pharmacological complexity of CKI is important for effective blockade of cancer migration and invasion.https://www.frontiersin.org/article/10.3389/fonc.2019.00314/fulltraditional chinese medicine (TCM)compound kushen injection (CKI)cell migrationinvasioncancergene regulatory networks
collection DOAJ
language English
format Article
sources DOAJ
author Saeed Nourmohammadi
Thazin Nwe Aung
Jian Cui
Jinxin V. Pei
Michael Lucio De Ieso
Yuka Harata-Lee
Zhipeng Qu
David L. Adelson
Andrea J. Yool
spellingShingle Saeed Nourmohammadi
Thazin Nwe Aung
Jian Cui
Jinxin V. Pei
Michael Lucio De Ieso
Yuka Harata-Lee
Zhipeng Qu
David L. Adelson
Andrea J. Yool
Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
Frontiers in Oncology
traditional chinese medicine (TCM)
compound kushen injection (CKI)
cell migration
invasion
cancer
gene regulatory networks
author_facet Saeed Nourmohammadi
Thazin Nwe Aung
Jian Cui
Jinxin V. Pei
Michael Lucio De Ieso
Yuka Harata-Lee
Zhipeng Qu
David L. Adelson
Andrea J. Yool
author_sort Saeed Nourmohammadi
title Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
title_short Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
title_full Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
title_fullStr Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
title_full_unstemmed Effect of Compound Kushen Injection, a Natural Compound Mixture, and Its Identified Chemical Components on Migration and Invasion of Colon, Brain, and Breast Cancer Cell Lines
title_sort effect of compound kushen injection, a natural compound mixture, and its identified chemical components on migration and invasion of colon, brain, and breast cancer cell lines
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2019-04-01
description Traditional Chinese Medicines are promising sources of new agents for controlling cancer metastasis. Compound Kushen Injection (CKI), prepared from medicinal plants Sophora flavescens and Heterosmilax chinensis, disrupts cell cycle and induces apoptosis in breast cancer; however, effects on migration and invasion remained unknown. CKI, fractionated mixtures, and isolated components were tested in migration assays with colon (HT-29, SW-480, DLD-1), brain (U87-MG, U251-MG), and breast (MDA-MB-231) cancer cell lines. Human embryonic kidney (HEK-293) and human foreskin fibroblast (HFF) served as non-cancerous controls. Wound closure, transwell invasion, and live cell imaging showed CKI reduced motility in all eight lines. Fractionation and reconstitution of CKI demonstrated combinations of compounds were required for activity. Live cell imaging confirmed CKI strongly reduced migration of HT-29 and MDA-MB-231 cells, moderately slowed brain cancer cells, and had a small effect on HEK-293. CKI uniformly blocked invasiveness through extracellular matrix. Apoptosis was increased by CKI in breast cancer but not in non-cancerous lines. Cell viability was unaffected by CKI in all cell lines. Transcriptomic analyses of MDA-MB-231indicated down-regulation of actin cytoskeletal and focal adhesion genes with CKI treatment, consistent with observed impairment of cell migration. The pharmacological complexity of CKI is important for effective blockade of cancer migration and invasion.
topic traditional chinese medicine (TCM)
compound kushen injection (CKI)
cell migration
invasion
cancer
gene regulatory networks
url https://www.frontiersin.org/article/10.3389/fonc.2019.00314/full
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