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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00314

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

  • 1University of Adelaide, Australia

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 no 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, consistent with observed impairment of cell migration. The pharmacological complexity of CKI is important for effective blockade of cancer migration and invasion.

Keywords: Migration, invasion, Cancer, Traditional Chinese Medicine, Compound kushen injection, alternative medicine, gene regulatory networks (GRN)

Received: 14 Feb 2019; Accepted: 08 Apr 2019.

Edited by:

Jiangjiang Qin, Zhejiang Chinese Medical University, China

Reviewed by:

Gang Cao, Zhejiang Chinese Medical University, China
Ying Wang, University of Macau, China
Songwei Duan, Harvard University, United States  

Copyright: © 2019 Nourmohammadi, Aung, Cui, Pei, De Ieso, Harata-lee, Qu, Adelson and Yool. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. David L. Adelson, University of Adelaide, Adelaide, Australia, david.adelson@adelaide.edu.au
Prof. Andrea J. Yool, University of Adelaide, Adelaide, Australia, andrea.yool@adelaide.edu.au