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

Turn off MathJax

Article Contents

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

PDF( 3612 KB)

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)

More Information

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

FullText(HTML)

References(13)

References

[1]	MURTAZA G, KARIM S, AKRAM MR, et al. Caffeic acid phenethyl ester and therapeutic potentials[J]. Biomed Res Int, 2014, 2014: 145342. DOI: 10.1155/2014/145342.
[2]	OLGIERD B, KAMILA Z, ANNA B, et al. The pluripotent activities of caffeic acid phenethyl ester[J]. Molecules, 2021, 26(5): 1335. DOI: 10.3390/molecules26051335.
[3]	LI M, WANG XF, SHI JJ, et al. Caffeic acid phenethyl ester inhibits liver fibrosis in rats[J]. World J Gastroenterol, 2015, 21(13): 3893-3903. DOI: 10.3748/wjg.v21.i13.3893.
[4]	YANG N, SHI JJ, WU FP, et al. Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway[J]. World J Gastroenterol, 2017, 23(7): 1203-1214. DOI: 10.3748/wjg.v23.i7.1203.
[5]	HAZARI Y, BRAVO-SAN PEDRO JM, HETZ C, et al. Autophagy in hepatic adaptation to stress[J]. J Hepatol, 2020, 72(1): 183-196. DOI: 10.1016/j.jhep.2019.08.026.
[6]	KOUROUMALIS E, VOUMVOURAKI A, AUGOUSTAKI A, et al. Autophagy in liver diseases[J]. World J Hepatol, 2021, 13(1): 6-65. DOI: 10.4254/wjh.v13.i1.6.
[7]	ALLAIRE M, RAUTOU PE, CODOGNO P, et al. Autophagy in liver diseases: Time for translation?[J]. J Hepatol, 2019, 70(5): 985-998. DOI: 10.1016/j.jhep.2019.01.026.
[8]	ROEHLEN N, CROUCHET E, BAUMERT TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives[J]. Cells, 2020, 9(4): 875. DOI: 10.3390/cells9040875.
[9]	KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166. DOI: 10.1038/s41575-020-00372-7.
[10]	LEVINE B, KROEMER G. Biological functions of autophagy genes: a disease perspective[J]. Cell, 2019, 176(1-2): 11-42. DOI: 10.1016/j.cell.2018.09.048.
[11]	WANG H, LIU Y, WANG D, et al. The upstream pathway of mTOR-mediated autophagy in liver diseases[J]. Cells, 2019, 8(12): 1597. DOI: 10.3390/cells8121597.
[12]	LEE KW, THIYAGARAJAN V, SIE HW, et al. Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells[J]. J Nutr Biochem, 2014, 25(9): 903-913. DOI: 10.1016/j.jnutbio.2014.04.001.
[13]	PARK M, KIM YH, WOO SY, et al. Tonsil-derived mesenchymal stem cells ameliorate CCl₄-induced liver fibrosis in mice via autophagy activation[J]. Sci Rep, 2015, 5: 8616. DOI: 10.1038/srep08616.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3) / Tables(2)

Get Citation

PDF

XML

Article Metrics

Article views (399) PDF downloads(37)

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

DOI: 10.3969/j.issn.1001-5256.2022.10.014

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

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

DOI: 10.3969/j.issn.1001-5256.2022.10.014

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content