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

Abstract

Introduction

Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified.

Methods

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.

Results

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.

Conclusion

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.

Keywords:

• cinnamaldehyde
• cancer-associated fibroblasts
• prostate cancer
• TLR4

Data Sharing Statement

The data is available from the corresponding authors on reasonable request.

Ethics Approval and Consent to Participate

All animal experiments were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health (Bethesda, MD, USA) and were approved by the Biological Research Ethics Committee, Institute of Biophysics, Chinese Academy of Sciences.

Disclosure

Yuanyuan Wang, Minghua Hu, Fangli Ma are employees of Infinitus Chinese Herbal Immunity Research Center, Infinitus China Company Ltd. The authors report no other possible conflicts of interest in this work.