Introduction:
Nasopharyngeal carcinoma (NPC) is a serious cancer with a poor prognosis and a significant risk of metastasis. Although its epigenetic control mechanisms are still unknown, epigallocatechin-3-gallate (EGCG) exhibits strong anticancer properties. Promoter methylation in malignancies often silences PACRG, a putative tumor suppressor gene. This study aimed to determine whether EGCG suppresses cancer by altering PACRG gene expression in NPC cells.

Material and methods:
NPC cells were subjected to EGCG or 5-aza-dC. Cellular functions were assessed by CCK-8, Transwell, and flow cytometry assays. Methylation-specific PCR (MSP) was used to identify PACRG promoter methylation, and gene expression was measured using quantitative real-time PCR (qRT-PCR) and Western blot (WB). The expression of DNA methyltransferase-related genes was evaluated. siRNA targeting PACRG was used to assess its functional involvement in the effects mediated by EGCG.

Results:
EGCG exerted dose- and time-dependent effects on NPC cells by reducing proliferation and migration while inducing apoptosis and G2 phase cell cycle arrest. Mechanistically, EGCG significantly reduced the mRNA expression and enzymatic activity of DNMT1, DNMT3A, and DNMT3B, resulting in decreased PACRG promoter methylation and restored PACRG expression. Functional assays revealed that knockdown of PACRG diminished the inhibitory effect of EGCG on NPC cells, indicating that the epigenetic reactivation of PACRG partially mediates the tumor-suppressive function of EGCG.

Conclusions:
Our results revealed that EGCG inhibits NPC progression by reducing PACRG promoter methylation, highlighting that PACRG demethylation and reactivation are a promising therapeutic strategy.