# Elucidating the potential carcinogenic molecular mechanisms of parabens in head and neck squamous cell carcinoma through network toxicology and molecular docking

## TL;DR

This study explores how parabens might cause head and neck cancer by analyzing their molecular effects and interactions with key genes.

## Contribution

The study introduces a novel network toxicology and molecular docking approach to uncover paraben-induced carcinogenic mechanisms in HNSCC.

## Key findings

- Eighty common targets were identified linking parabens to HNSCC, with 12 hub genes involved in cell cycle and p53 signaling.
- CCNA1 was validated as a poor survival prognostic factor in HNSCC and showed strong paraben binding.
- Parabens may hinder immune responses by reducing CD8+ T cell and B cell infiltration in HNSCC.

## Abstract

This study aims to systematically investigate the molecular mechanisms through which parabens may contribute to head and neck squamous cell carcinoma (HNSCC) carcinogenesis using integrated network toxicology and molecular docking.

Six commonly used parabens (ethyl-, propyl-, methyl-, heptyl-, butyl-, and benzylparaben) were selected for toxicity prediction via ProTox 3.0 and ADMETlab2.0. Their potential targets were retrieved from Swiss Target Prediction, ChEMBL, and the Similarity Ensemble Approach (SEA). HNSCC-related targets were collected from GeneCards, OMIM, and CTD, while differentially expressed genes (DEGs) were identified using TCGA-HNSC data. Functional enrichment, protein-protein interaction (PPI) network construction, hub gene identification, molecular docking, and immune infiltration analyses were performed using DAVID, STRING, Cytoscape, CB-DOCK2, and TIMER2.0.

We identified 80 common targets through which parabens may exert toxic effects in HNSCC. Among these, 12 hub genes (CCNB1, CDK1, CCNA2, CDK2, CDK4, TYMS, AURKA, CCNA1, CHEK1, CCNB2, PLK1, CDC25A) were significantly overexpressed in HNSCC tissues and were primarily enriched in cell cycle regulation, p53 signaling, and viral carcinogenesis pathways. CCNA1 was further validated as an independent prognostic factor associated with poor survival. Molecular docking revealed strong binding affinities between parabens and hub proteins. Immune infiltration analysis indicated a negative correlation between CCNA1 expression and CD8 + T cell and B cell infiltration.

Parabens may promote HNSCC progression by disrupting cell cycle regulation and immune responses via direct interactions with key hub genes. These findings provide a novel mechanistic basis for the carcinogenic potential of parabens in HNSCC and underscore the need for further experimental and epidemiological validation.