1. Academic Validation
  2. Ligustilide promotes apoptosis of cancer-associated fibroblasts via the TLR4 pathways

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.
Jing Ma 1 Jie Mei 2 Jia Lu 2 Yuanyuan Wang 3 Minghua Hu 3 Fangli Ma 3 Hanan Long 4 Zhihai Qin 5 Ning Tao 6
Affiliations

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.
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.

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