Ligustilide promotes apoptosis of cancer-associated fibroblasts via the TLR4 pathways

Jing Ma; Jie Mei; Jia Lu; Yuanyuan Wang; Minghua Hu; Fangli Ma; Hanan Long; Zhihai Qin; Ning Tao

doi:10.1016/j.fct.2019.110991

Ligustilide promotes apoptosis of cancer-associated fibroblasts via the TLR4 pathways

Food Chem Toxicol. 2020 Jan:135:110991. doi: 10.1016/j.fct.2019.110991. Epub 2019 Nov 22.

Authors

Jing Ma¹, Jie Mei², Jia Lu², Yuanyuan Wang³, Minghua Hu³, Fangli Ma³, Hanan Long⁴, Zhihai Qin⁵, Ning Tao⁶

Affiliations

¹ Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, China.
² Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
³ Infinitus Chinese Herbal Immunity Research Centre, Infinitus China Company Ltd, Guangzhou, China.
⁴ School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, China. Electronic address: longhanan@swmu.edu.cn.
⁵ Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, China; College of Life Science, University of the Chinese Academy of Sciences, Beijing, China. Electronic address: zhihai@ibp.ac.cn.
⁶ Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: tao@ibp.ac.cn.

PMID: 31765699
DOI: 10.1016/j.fct.2019.110991

Abstract

The goal of this research was to study the selective pro-apoptotic effect of ligustilide on prostate-cancer-associated fibroblast in the tumor microenvironment and the related molecular mechanisms. The effects of ligustilide on cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) isolated from the prostate were determined by MTT assay. Flow cytometry and cellular immunofluorescence were used to detect the effects of ligustilide on the cell cycle and apoptosis. Western blotting was used to detect the expression of apoptosis-related proteins after the action of ligustilide on CAFs. In the investigation, ligustilide had a selective pro-apoptotic effect on prostate-CAFs. After ligustilide treatment, the proportion of CAFs in the G2-M phase of the cell cycle increased, and the expression of apoptosis-related proteins (p-P53, Bcl-2, Caspase9 and Cytochrome C) changed. Ligustilide blocks the CAF cell cycle and induces the apoptosis of CAFs.

Keywords: Apoptosis; Cell cycle; Fibroblast; Ligustilide; Tumor microenvironment.

MeSH terms

4-Butyrolactone / analogs & derivatives*
4-Butyrolactone / pharmacology
Animals
Apoptosis / drug effects*
Cancer-Associated Fibroblasts / drug effects*
Cell Cycle / drug effects
Cell Proliferation / drug effects
Heterografts
Humans
Male
Mice
Mice, Inbred C57BL
Prostatic Neoplasms / pathology*
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism*
Tumor Microenvironment

Substances

TLR4 protein, human
Toll-Like Receptor 4
ligustilide
4-Butyrolactone