Identification of candidate anti-cancer molecular mechanisms of Compound Kushen Injection using functional genomics
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Zhipeng Qu1, Jian Cui1,*, Yuka Harata-Lee1,*, Thazin Nwe Aung1, Qianjin Feng2, Joy M. Raison1, Robert Daniel Kortschak1, David L. Adelson1
1Department of Genetics and Evolution, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia
2Shanxi Modern Chinese Medicine Engineering Laboratory, Shanxi University of Traditional Chinese Medicine, Shanxi 030619, China
*These authors contributed equally to this work
David L. Adelson, email: firstname.lastname@example.org
Keywords: systems biology, traditional Chinese medicine, lncRNA, transcriptome
Received: March 02, 2016 Accepted: August 24, 2016 Published: September 01, 2016
Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively. Transcriptome data of cells treated with CKI or 5-Fluorouracil (5-FU) for 24 and 48 hours were subsequently acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.
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