Modifying effects of nerolidol on cell surface glycoconjugates and suppressed inflammation during DMBA-induced oral carcinogenesis: An in vivo and in silico

Oral squamous cell carcinomas (OSCC) were created in the buccal pouches of golden Syrian hamsters by painting them three times a week with 0.5% DMBA in liquid paraffin for 12 weeks. The objective of this study was to evaluate the effects of nerolidol (NER) on the expression of inflammatory markers (TNF-α, NF-κB, and COX-2) and cell surface glycoconjugates in DMBA-induced hamster buccal pouch cancer. In DMBA alone treated hamsters, we observed 100% of well-differentiated OSCC development, changes in inflammation-related protein expression and abnormalities of glycoconjugates levels compared to control hamsters. Oral administration of NER (50 and 100 mg/kg body weight) restored the immunohistoexpression of inflammatory protein (TNF-α, NF-κB and COX-2) and glycoconjugates status in DMBA-induced buccal pouch hamsters. In addition, we used in-silico analysis to predict the nature of interactions when NER targeted inflammatory proteins (TNF-α, NF-κB and COX-2). The docking analysis of NER has low binding energy and higher binding affinity to bind with the above inflammatory markers. The stability of NER docked COX-2 protein complex was confirmed by molecular dynamics simulation using Desmond module of Schrodinger. Thus, the present study suggests that NER potentially prevented the altered immunohistoexpression of TNF-α, NF-κB and COX-2 proteins and abnormalities of cell surface glycoconjugates level in DMBA-induced oral cancer.