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Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress.

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机构： [a]School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, 646000, China [b]Beijing National Day School, Beijing, 100101, China [c]College of Life Science, University of the Chinese Academy of Sciences, Beijing, 100101, China [d]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China [e]The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China

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关键词： Curcumin Cancer-associated fibroblasts ROS Apoptosis Endoplasmic reticulum stress

摘要：

Cancer-associated fibroblasts (CAFs) play an important role in tumorigenesis, development, and migration. Eliminating CAFs or reducing their tumor-promoting activity is beneficial for tumor immunotherapy. Curcumin is a natural polyphenol derived from turmeric, which has been shown to inhibit the growth of many types of tumor. In this study, we explored the effect of curcumin on prostate-CAFs and its underlying molecular mechanism. The effect of curcumin on CAFs was measured using MTT assay and plate colony formation assay. Flow cytometry was used to detect cell apoptosis, ROS, Cell cycle, and mitochondrial membrane potential (ΔΨm) changes after curcumin treatment. Western Blot was used to detect changes in expression levels of related proteins in CAFs after curcumin stimulation. Colorimetry was used to detect the change of caspase 3 activity. The mRNA levels of Bims, Puma, ATF4 and CHOP were determined by qRT-PCR. We found that curcumin induced the apoptosis and cell cycle arrest of CAFs, which is mainly caused by the ROS-mediated endoplasmic reticulum stress pathway. For mechanism, the up-regulation of ROS caused by curcumin triggers endoplasmic reticulum stress of CAFs through the PERK-eIF2α-ATF4 axis. Our study suggests that curcumin selectively inhibits prostate-CAFs by inducing apoptosis and cell cycle arrest in G2-M phase, indicating a novel application of curcumin in tumor therapy. Copyright © 2020 Elsevier Inc. All rights reserved.

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出版当年[2020]版：

大类 | 3 区生物学

小类 | 3 区生化与分子生物学 3 区生物物理

最新[2023]版：

大类 | 3 区生物学

小类 | 2 区生物物理 3 区生化与分子生物学

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第一作者机构： [a]School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, 646000, China

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通讯机构： [a]School of Basic Medical Sciences of Southwest Medical University, Luzhou, Sichuan, 646000, China [c]College of Life Science, University of the Chinese Academy of Sciences, Beijing, 100101, China [d]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China [e]The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China [*1]Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang District, Beijing City, China

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Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress.

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