Cinnamaldehyde Treatment of Prostate Cancer-Associated Fibroblasts Prevents Their Inhibitory Effect on T Cells Through Toll-Like Receptor 4.

Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified.
To test the effect of cinnamaldehyde on prostate CAFs, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide assay was used to determine their survival. When spleen cells were treated with CAF supernatant, the proliferation of T cells was inhibited as determined by flow cytometry. After cinnamaldehyde treatment, this immunosuppressive function of CAFs was partially reversed. To explore the molecular mechanism, Western blotting and the quantitative real-time polymerase chain reaction were applied, and TLR4-dependent signaling pathway-related protein and mRNA levels were quantified.
Cinnamaldehyde acted on the TLR4-dependent signaling pathway, altering the function of CAFs such that its supernatant no longer inhibited the proliferation of T cells.
These data indicate that cinnamaldehyde can modify the functions of CAFs, which may be helpful for treating tumors. Cinnamaldehyde can suppress CAF T-cell inhibition.
AuthorsJie Mei, Jing Ma, Yuwei Xu, Yuanyuan Wang, Minghua Hu, Fangli Ma, Zhihai Qin, Rui Xue, Ning Tao
JournalDrug design, development and therapy (Drug Des Devel Ther) Vol. 14 Pg. 3363-3372 ( 2020) ISSN: 1177-8881 [Electronic] New Zealand
PMID32884240 (Publication Type: Journal Article)
Copyright© 2020 Mei et al.
Chemical References
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Acrolein
  • cinnamaldehyde
  • Acrolein (analogs & derivatives, pharmacology)
  • Animals
  • Cancer-Associated Fibroblasts (drug effects, metabolism, pathology)
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prostatic Neoplasms (drug therapy, metabolism, pathology)
  • Signal Transduction (drug effects)
  • Structure-Activity Relationship
  • T-Lymphocytes (drug effects, metabolism)
  • Toll-Like Receptor 4 (antagonists & inhibitors, metabolism)
  • Tumor Cells, Cultured

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