Role and mechanism of caffeic acid phenethyl ester in hepatic stellate cell

Ning YANG; Jiang DENG; Yikai WANG; Sha CHANG; Ning GAO; Wenjun WANG; Shuangsuo DANG; Juanjuan SHI

doi:10.3969/j.issn.1001-5256.2022.10.014

Volume 38 Issue 10

Oct. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(10): 2273-2278

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Role and mechanism of caffeic acid phenethyl ester in hepatic stellate cell

DOI: 10.3969/j.issn.1001-5256.2022.10.014

1.
Department of Cancer, The Affiliated Hospital of Shanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China
2.
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China

Research funding:

Shaanxi Key Research and Development Project (2021SF-227);

Fundamental Research Funds for the Central Universities (xjh012019063)

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Corresponding author: SHI Juanjuan, shijuan0307@163.com(ORCID: 0000-0002-5626-9821)
Received Date: 2022-03-15
Accepted Date: 2022-04-21
Published Date: 2022-10-20

Abstract

Abstract

Objective To assess the effect and underlying molecular events of caffeic acid phenethyl ester (CAPE) on rat hepatic stellate HSC-T6 cells. Methods HSC-T6 cells were grown and treated with different concentrations of CAPE (5, 10, or 15 μmol/L), transfected with or without LC3-GFP plasmid, and then treated with or without an autophagy inducer rapamycin or the autophagy inhibitor 3-methyladenine (3-MA). The changed cell viability and morphology were assessed by using cell viability MTT assay and Transmission electron microscope, respectively. The expression of LC3 protein in HSC-T6 cells was detected by immunofluorescence assay, the autophagy-related genes expression of ATG5, ATG7, ATG12, Beclin1 and LC3 were detected by qRT-PCR, and the expression of ATG7, Beclin1, LC3I/Ⅱ, p-AKT/AKT, p-mTOR protein was detected by Western-blot. Comparison between multiple groups was analyzed by one-way ANOVA with Dunnett t-test. Results Compared with the control, CAPE treatment significantly reduced cell viability but induced formation of lipid droplets and roulette-shaped autophagosomes. Compared with the control (13.34%±2.59), LC3 protein was significantly induced in HSC-T6 cells after CAPE treatment (5 μmol/L, 23.68%±3.76, t=-5.553, P < 0.001; 10 μmol/L, 43.47%±3.83, t=-15.958, P < 0.001; 15 μM, 57.25%±2.78, t=-28.334, P < 0.001), while levels of ATG5, ATG7, ATG12, Beclin 1, and LC3 mRNAs were all significantly increased in 10 μm and 15 μm CAPE treated cells vs the control (all P < 0.05). After LC3 overexpression in HSC-T6 cells, LC3 protein was induced vs the vector control (79.01%±6.69% vs 67.06%±6.74%, t=-3.083, P=0.012), while rapamycin treatment further increased LC3 expression (86.88%±5.42%, t=-2.239, P=0.049); however, 3-MA treatment significantly decreased LC3 expression in cells (71.22%±4.29%, t=-2.404, P=0.037). In addition, levels of ATG7, Beclin1, and LC3 Ⅰ/Ⅱ proteins were increased, whereas levels of AKT/p-AKT and p-mTOR were decreased in the CAPE and rapamycin groups vs controls. However, the 3-MA treatment had an opposite result, indicating that 3-MA reversed CAPE-induced effects in HSC-T6 cells. Conclusion Caffeic acid phenethyl ester may induce autophagy to reduce cell viability in hepatic stellate cells by inhibition of the AKT/mTOR signaling.
- Liver Cirrhosis,
- Caffeic Acids,
- Hepatic Stellate Cell

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Role and mechanism of caffeic acid phenethyl ester in hepatic stellate cell

DOI: 10.3969/j.issn.1001-5256.2022.10.014