TY - JOUR
T1 - Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis
AU - Yang, Bowen
AU - Wang, Neng
AU - Wang, Shengqi
AU - Li, Xiong
AU - Zheng, Yifeng
AU - Li, Min
AU - Song, Juxian
AU - Zhang, Fengxue
AU - Mei, Wenjie
AU - Lin, Yi
AU - Wang, Zhiyu
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China [grant numbers 81703749, 81873306, 81573651 and 81703764], Guangdong Science and Technology Department (2016A030306025), Guangzhou Science, Technology and Innovation Commission (805296345055), Pearl River S&T Nova Program of Guangzhou (201506010098), Combined Scientific Project Funded by Guangdong Provincial Science and Technology Agency and Guangdong Provincial Academy of Traditional Chinese Medicine (2014A020221047), Guangdong High-level University Construction Project (A1-AFD018161Z1510, A1-AFD018171Z11102 and A1-AFD018171Z11101), Guangdong High-level Personnel of Special Support Program (A1-3002-16-111-003), Guangdong traditional Chinese medicine bureau project (20181132 and 20182044), the Post-doctoral Science Foundation of China (2017M612644, 2018T110861 and 2017M622669), the PhD Start-up Fund of Natural Science Foundation of Guangdong Province (2017A030310213) and Guangdong provincial key project (2016kzdxm032), Science and Technology Planning Project of Guangdong Province (2017B030314166), the Specific Research Fund for TCM Science and Technology of Guangdong provincial Hospital of Chinese Medicine (YN2018MJ07, YN2018QJ08).
Publisher copyright:
© 2019 The Authors. Published by Elsevier Masson SAS.
PY - 2019/4
Y1 - 2019/4
N2 - BackgroundBreast 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. MethodsMultiple molecular biology experiments as well as network pharmacology, bioinformatics analysis were conducted to investigate the anti-metastasis mechanism of Oldenlandia diffusa in breast cancer. ResultsWe 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. ConclusionsOverall, 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.
AB - BackgroundBreast 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. MethodsMultiple molecular biology experiments as well as network pharmacology, bioinformatics analysis were conducted to investigate the anti-metastasis mechanism of Oldenlandia diffusa in breast cancer. ResultsWe 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. ConclusionsOverall, 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.
KW - Bioinformatics analysis
KW - Breast cancer
KW - Caveolin-1
KW - Metastasis
KW - Network pharmacology
KW - Oldenlandia diffusa
UR - http://www.scopus.com/inward/record.url?scp=85061816884&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2019.108607
DO - 10.1016/j.biopha.2019.108607
M3 - Journal article
C2 - 30784915
AN - SCOPUS:85061816884
SN - 0753-3322
VL - 112
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 108607
ER -