Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis

Fengyang Jing; Lijing Zhu; Jiaying Bai; Xinjia Cai; Xuan Zhou; Jianyun Zhang; Heyu Zhang; Tiejun Li

doi:10.1016/j.archoralbio.2023.105740

Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis

Arch Oral Biol. 2023 Sep:153:105740. doi: 10.1016/j.archoralbio.2023.105740. Epub 2023 Jun 5.

Authors

Fengyang Jing¹, Lijing Zhu¹, Jiaying Bai², Xinjia Cai¹, Xuan Zhou¹, Jianyun Zhang³, Heyu Zhang⁴, Tiejun Li⁵

Affiliations

¹ Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing 100081, China.
² Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China.
³ Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing 100081, China. Electronic address: jianyunz0509@aliyun.com.
⁴ Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing 100081, China. Electronic address: zhangheyu1983@sina.cn.
⁵ Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing 100081, China. Electronic address: litiejun22@vip.sina.com.

PMID: 37354753
DOI: 10.1016/j.archoralbio.2023.105740

Abstract

Objectives: To reveal the mechanisms underlying the epigallocatechin-3-gallate (EGCG)-mediated inhibition of carcinogenesis and the related regulatory signaling pathways.

Design: The effect of EGCG on the proliferation of OSCC cells was examined. SuperPred, ChEMBL, Swiss TargetPrediction, DisGeNET, GeneCards, and National Center for Biotechnology Information databases were used to predict the EGCG target genes and oral leukoplakia (OL)-related, oral submucosal fibrosis (OSF)-related, and OSCC-related genes. The binding of EGCG to the target proteins was simulated using AutoDock and PyMOL. The Cancer Genome Atlas (TCGA) dataset was subjected to consensus clustering analysis to predict the downstream molecules associated with these targets, as well as their potential functions and pathways.

Results: EGCG significantly inhibited OSCC cell proliferation (p < 0.001). By comparing EGCG target genes with genes linked to oral potentially malignant disorder (OPMD) and OSCC, a total of eleven potential EGCG target genes were identified. Furthermore, EGCG has the capacity to bind to eleven proteins. Based on consensus clustering and enrichment analysis, it is suggested that EGCG may hinder the progression of cancer by altering the cell cycle and invasive properties in precancerous lesions of the oral cavity. Some possible strategies for modifying the cell cycle and invasive properties may include EGCG-mediated suppression of specific genes and proteins, which are associated with cancer development.

Conclusions: This study investigated the molecular mechanisms and signaling pathways associated with the EGCG-induced suppression of OSCC. The identification of specific pharmacological targets of EGCG during carcinogenesis is crucial for the development of innovative combination therapies involving EGCG.

Keywords: Epigallocatechin-3-gallate; Oral leukoplakia; Oral squamous cell carcinoma; Oral submucosal fibrosis.

MeSH terms

Carcinogenesis
Catechin* / pharmacology
Catechin* / therapeutic use
Cell Line, Tumor
Epithelial Cells / metabolism
Humans
Mouth Neoplasms* / pathology
Oral Submucous Fibrosis*
Signal Transduction

Substances

epigallocatechin gallate
Catechin