Abstract

BackgroundLiquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine. In the previous study we found the anti-breast cancer effect of triterpenoid in Liquidambaris Fructus. This study is a further investigation of the triterpenoids in Liquidambaris Fructus and aims to identify their anti-breast cancer targets, meanwhile, to estimate the rationality of the traditional applications of Liquidambaris Fructus.MethodsTriterpenoids in Liquidambaris Fructus were isolated and their structures were identified by NMR spectrums. Potential targets of these triterpenoids were predicted using a reverse pharmacophore mapping strategy. Associations between these targets and the therapeutic targets of breast cancer were analyzed by constructing protein-protein interaction network, and targets played important roles in the network were identified using Molecular Complex Detection method. Binding affinity between the targets and triterpenoids was studied using molecular docking method. Gene ontology enrichment analysis was conducted to reveal the biological process and signaling pathways that the identified targets were involved in.ResultsThirteen triterpenoids were identified and 6 of them were the first time isolated from Liquidambaris Fructus. Predicted ADME properties revealed a good druggability of these triterpenoids. We identified 18 protein targets which were closely related to breast cancer progression, especially triple-negative, basal-like or advanced stage breast cancers. The triterpenoids could bind with these targets as their inhibitors: hydrophobic skeleton is a favorable factor for them to stabilize at binding site and polar C17- or C3- substituent was necessary for binding. GO enrichment analysis indicated that inhibition of protein tyrosine kinases autophosphorylation might be the primary mechanism for the anti-breast cancer effect of the triterpenoids, and ErbB4 and EGFR were the most relevant targets.ConclusionsThe study revealed that triterpenoids from Liquidambaris Fructus might exert anti-breast cancer effect by directly inhibit multiple protein targets and signaling pathways, especially ErbB4 and EGFR and related pathways. This study also brings up another hint that the traditional applications of Liquidambaris Fructus on hypogalactia should be reassessed systematically because it might suppress rather than promote lactation by inhibiting the activity of ErbB4.

Highlights

  • Liquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine

  • In the previous research we found that betulonic acid, a triterpenoid come from Liquidambaris Fructus (LF), could inhibit human breast cancer MCF7 cells proliferation, and induce the cell cycle arrest and apoptosis [6]

  • Among the 20 triterpenoids, LF01, LF04, LF08, LF09 and LFa belong to lupane-type triterpenoids, and LF06, LFg belong to ursane-type triterpenoids, and the others are oleanane-type triterpenoids (Fig. 1)

Read more

Summary

Introduction

Liquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine. In the previous study we found the anti-breast cancer effect of triterpenoid in Liquidambaris Fructus. This study is a further investigation of the triterpenoids in Liquidambaris Fructus and aims to identify their anti-breast cancer targets, to estimate the rationality of the traditional applications of Liquidambaris Fructus. LF is believed to unclog the meridians (Jingluo) in Traditional Chinese Medicine, and because it mainly affect the liver meridian which is considered closely related to mammary function, LF has been used to treat some breast disease such as hypogalactia [1], mastitis [2], mammary duct ectasia [3], mammary gland hyperplasia [4], etc.

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call