Cancers 2019, 11(1), 91; https://doi.org/10.3390/cancers11010091
The Potential Mechanism of Bufadienolide-Like Chemicals on Breast Cancer via Bioinformatics Analysis
Yingbo Zhang 1,2,†, Xiaomin Tang 3,†, Yuxin Pang 3,4,*
, Luqi Huang 4,*
, Dan Wang 1,2, Chao Yuan 1,2
, Xuan Hu 1,2 and Liping Qu 5
, Xuan Hu 1,2 and Liping Qu 5
1
Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou 571737, China
2
Hainan Provincial Engineering Research Center for Blumea Balsamifera, Danzhou 571737, China
3
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China
4
National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
5
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
â€
The author had the same contribution to this work.
*
Authors to whom correspondence should be addressed.
Received: 28 November 2018 / Revised: 20 December 2018 / Accepted: 8 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Application of Bioinformatics in Cancers)
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Abstract
Bufadienolide-like chemicals are mostly composed of the active ingredient of Chansu and they have anti-inflammatory, tumor-suppressing, and anti-pain activities; however, their mechanism is unclear. This work used bioinformatics analysis to study this mechanism via gene expression profiles of bufadienolide-like chemicals: (1) Differentially expressed gene identification combined with gene set variation analysis, (2) similar small -molecule detection, (3) tissue-specific co-expression network construction, (4) differentially regulated sub-networks related to breast cancer phenome, (5) differentially regulated sub-networks with potential cardiotoxicity, and (6) hub gene selection and their relation to survival probability. The results indicated that bufadienolide-like chemicals usually had the same target as valproic acid and estradiol, etc. They could disturb the pathways in RNA splicing, the apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway, and protein folding. We also investigated the potential cardiotoxicity and found a dysregulated subnetwork related to membrane depolarization during action potential, retinoic acid receptor binding, GABA receptor binding, positive regulation of nuclear division, negative regulation of viral genome replication, and negative regulation of the viral life cycle. These may play important roles in the cardiotoxicity of bufadienolide-like chemicals. The results may highlight the potential anticancer mechanism and cardiotoxicity of Chansu, and could also explain the ability of bufadienolide-like chemicals to be used as hormones and anticancer and vasoprotectives agents.
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Zhang, Y.; Tang, X.; Pang, Y.; Huang, L.; Wang, D.; Yuan, C.; Hu, X.; Qu, L. The Potential Mechanism of Bufadienolide-Like Chemicals on Breast Cancer via Bioinformatics Analysis. Cancers 2019, 11, 91.
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