PUBLICATION
Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis
- Authors
- Yang, B., Wang, N., Wang, S., Li, X., Zheng, Y., Li, M., Song, J., Zhang, F., Mei, W., Lin, Y., Wang, Z.
- ID
- ZDB-PUB-190221-7
- Date
- 2019
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 112: 108607 (Journal)
- Registered Authors
- Keywords
- Bioinformatics analysis, Breast cancer, Caveolin-1, Metastasis, Network pharmacology, Oldenlandia diffusa
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents, Phytogenic/isolation & purification
- Antineoplastic Agents, Phytogenic/pharmacology*
- Antineoplastic Agents, Phytogenic/therapeutic use
- Breast Neoplasms/drug therapy
- Breast Neoplasms/metabolism*
- Breast Neoplasms/pathology*
- Caveolin 1/antagonists & inhibitors
- Caveolin 1/biosynthesis*
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Drug Delivery Systems/methods*
- Drugs, Chinese Herbal/isolation & purification
- Drugs, Chinese Herbal/pharmacology*
- Drugs, Chinese Herbal/therapeutic use
- Female
- Humans
- Oldenlandia*
- Xenograft Model Antitumor Assays/methods
- Zebrafish
- PubMed
- 30784915 Full text @ Biomed. Pharmacother.
Citation
Yang, B., Wang, N., Wang, S., Li, X., Zheng, Y., Li, M., Song, J., Zhang, F., Mei, W., Lin, Y., Wang, Z. (2019) Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 112:108607.
Abstract
Background Breast cancer remains the most common female malignancy and metastasis is the leading cause of death in breast cancer patients. Oldenlandia diffusa has been empirically and extensively used as an adjuvant therapy for metastatic breast cancer patients in Traditional Chinese Medicine (TCM) with proven efficacy. However, its anti-metastasis mechanism has been poorly revealed.
Methods Multiple molecular biology experiments as well as network pharmacology, bioinformatics analysis were conducted to investigate the anti-metastasis mechanism of Oldenlandia diffusa in breast cancer.
Results We demonstrated that ethanol extract of Oldenlandia diffusa (EEOD) significantly inhibited proliferation and induced apoptosis of high-metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-453, while having no obvious cytotoxic effect on multiple nonmalignant cells. Furthermore, EEOD remarkably suppressed the migration and invasion capacities of the above breast cancer cells by modulating the matrix metalloproteinases (MMPs) and the epithelial-mesenchymal transition (EMT) pathway. More importantly, EEOD also significantly inhibited breast cancer metastasis in zebrafish xenotransplantation model in vivo. Network pharmacology and bioinformatics analysis further demonstrated that EEOD yielded 12 candidate compounds and 225 potential targets, and shared 85 putative targets associated with breast cancer metastasis. Mechanistically, RNA sequencing and experimental validation results suggested that EEOD might inhibit breast cancer metastasis by attenuating the expression of caveolin-1 (Cav-1) as overexpression of Cav-1 could weaken the anti-metastasis efficacy of EEOD.
Conclusions Overall, our findings proved that EEOD could inhibit breast cancer metastasis by attenuating the expression of Cav-1, highlighting the use of EEOD as an adjunctive therapy for metastatic breast cancer patients. This study also provides novel insights into network pharmacology and bioinformatics analysis as effective tools to illuminate the scientific basis of TCM.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping