PLAGL1 Gene Demethylation Induced by Epigallocatechin Gallate Promotes Pheochromocytoma Cell Apoptosis Via Wnt/β-catenin Signaling Pathway

He, Chunling; Zhou, Jue; Wang, Dong; Wang, Ruoling; Wu, Mingcai; Dong, Ting

doi:10.31557/APJCP.2022.23.6.2119

PLAGL1 Gene Demethylation Induced by Epigallocatechin Gallate Promotes Pheochromocytoma Cell Apoptosis Via Wnt/β-catenin Signaling Pathway

Document Type : Research Articles

Authors

¹ Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China.

² School of Basic Medical Sciences, Wannan Medical College, Wuhu, Anhui, China.

³ Department of Hepatobiliary surgery, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China.

⁴ Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.

10.31557/APJCP.2022.23.6.2119

Abstract

Objective: The aim of this study was to investigate the expression and the promoter methylation level of PLAGL1 gene and the mechanism of epigallocatechin gallate (EGCG) that induces PLAGL1 gene demethylation and promotes the apoptosis of pheochromocytoma (PCC) in PC12 cell line. Methods: The PC12 cells were treated with 25, 50, 75, 100, and 150 μg/mL EGCG for 48 hours. MSP was used to examine PLAGL1 gene methylation and an MTT assay was performed to detect the cell proliferation. The cell apoptosis was detected using flow cytometry. The mRNA and protein expressions of DNMT1, PLAGL1, Wnt, and β-catenin were detected using RT-quantitative PCR and Western blot. Results: EGCG dose-dependently reduced the cell viability and reversed PLAGL1 gene hypermethylation in PC12 cells (P<0.05). The cell apoptosis was significantly increased in PC12 cells treated with EGCG. The EGCG treatment restored the expressions of PLAGL1 and downregulated the expression of DNMT1, Wnt, and β-catenin in PC12 cells (P<0.05). Conclusion: The EGCG induces the demethylation process of PLAGL1 gene through down-regulating DNMT1 and restores the PLAGL1 mRNA and protein expression. The Wnt/β-catenin signaling pathway is involved in the regulation of PCC cell apoptosis promoted by EGCG inducing PLAGL1 gene demethylation.

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