Insilico Insight into the Association between Polycyclic Aromatic Hydrocarbons and Human Toll like Receptor in Progression of Esophageal Carcinogenesis

Abstract

Cancer creates enormous burden and is a leading cause of death in most of the countries. Esophageal cancer (EC) is one of the most common cancers in the world and has the worst survival of all cancers. Esophageal Squamous Cell Carcinoma (ESCC) and adenocarcinoma are the two main types of esophageal cancer. Exposure of polycyclic aromatic hydrocarbons (PAHs) can be cited as one of the reasons for development of Esophageal Squamous Cell Carcinoma. Toll Like Receptors (TLRs) present in human esophageal epithelial cells may pose a major role in pathogen recognition, activation of innate immunity and cancer. The study attempts to predict the role of carcinogenic PAHs in TLR4 signaling pathway and how it can ultimately result in immuno suppression and development of esophageal cancer by insilico docking evaluation. For the study we retrieved the structure of sixteen PAHs from the PubChem database and the protein model of TLR4 (PDB ID: 4G8A) from protein data bank (PDB). The binding affinity of PAHs to the TLR4 receptor was calculated using molecular docking software Auto Dock1.5. The results showed that Benzo[a]pyrene showed strong interaction toward TLR4 receptor with the highest number of polar contacts along with high binding affinity values. Considering the presence of Benzo[a] pyrene in different environmental, occupational and behavioral sources globally, there is a need for future research on the risk assessment of Benzo[a]pyrene on Esophageal Squamous Cell Carcinoma.

Keywords:

• Docking
• esophageal cancer
• immuno suppression
• PAHs
• TLR4 signaling

Disclosure statement

There are no conflicts of interest.