Cinnamaldehyde induces endogenous apoptosis of the prostate cancer-associated fibroblasts via interfering the Glutathion
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ORIGINAL PAPER
Cinnamaldehyde induces endogenous apoptosis of the prostate cancer‑associated fibroblasts via interfering the Glutathione‑associated mitochondria function Le Han1 · Jie Mei2 · Jing Ma3 · Fazhan Wang4 · Zhuoyu Gu4 · Jianru Li1 · Zhiwei Zhang2 · Yanqiong Zeng3 · Xiaohan Lou4 · Xiaohan Yao4 · Ning Tao1 · Zhihai Qin1,2,3,4 Received: 9 May 2020 / Accepted: 4 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Cinnamaldehyde (CA) is an essential component of cinnamon that has been shown to exhibit anti-tumor effects through growth inhibition and induction of apoptosis in cancer cells. We have previously shown that CA could interfere with myeloidderived suppressor cells (MDSCs), leading to cancer growth inhibition. In addition, recent studies have demonstrated that cancer-associated fibroblasts (CAFs) promote cancer development in different ways. However, the effect of CA in CAFs has not been studied. In this study, we investigated the effect and mechanism of action of CA in prostate CAFs. We found that CA induced cell cycle arrest and apoptosis in prostate CAFs via the intrinsic pathway. This was due to the decrease in mitochondrial membrane potential (∆Mψ), increased level of intracellular reactive oxygen species (ROS), and calcium ion (Ca2+). In addition, protein expression analysis showed an increase in the expression levels of cytochrome c, bax, cleaved caspase 3 and cleaved PARP, and a decrease in the expression levels of Bcl-2, caspase 9, PARP, and DEF-45. Interestingly, reduced glutathione (GSH) rescued CAFs from CA-induced cell apoptosis, demonstrating that generation of ROS is critical for this effect. From this study, we see that CA has the ability to inhibit growth of CAFs and is therefore a potential cancer therapeutic target. Keywords Prostate cancer-associated fibroblasts · Cinnamaldehyde · Apoptosis · Mitochondria · Glutathione
Introduction Le Han and Jie Mei have contributed equally to the manuscript. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12032-020-01417-2) contains supplementary material, which is available to authorized users. * Ning Tao [email protected] * Zhihai Qin [email protected] 1
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang Area, Beijing 100101, China
2
College of Life Science, University of the Chinese Academy of Sciences, Beijing 100101, China
3
School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, Sichuan, China
4
The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan, China
Cinnamaldehyde (CA) is an essential component of cinnamon, that has been used in the practice of Chinese medicine for thousands of years [1]. Among all the ingredients of cassia, CA is the only one that has been shown to have antimicrobial and anti-tumor effects. It induces antimicrobial effects by damaging the integrity of th
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