Network pharmacology and RNA sequencing studies on triterpenoid saponins from Bupleurum chinense for the treatment of breast cancer

Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast...

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Bibliographic Details
Published in:RSC advances 2019-12, Vol.9 (70), p.41088-41098
Main Authors: Li, Danqi, Liu, Da, Yue, Dandan, Gao, Pinyi, Du, Cheng, Liu, Xuegui, Zhang, Lixin
Format: Article
Language:English
Subjects:
Apoptosis
Biocompatibility
Bioinformatics
Biological activity
Breast cancer
Chemistry
Cytotoxicity
Formulations
Gene sequencing
Kinases
Network analysis
Pharmacology
Proteins
Ribonucleic acid
RNA
Saponins
Signaling
Toxicity
Tyrosine
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Summary:Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both and experiments. Saikosaponin compounds are the characteristic constituent of , which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of . In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3'',6''- -diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6''- -acetylsaikosaponin-b (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.
ISSN:2046-2069
2046-2069
DOI:10.1039/c9ra08970e