Abstract
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.
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Abbreviations
- NER:
-
Nerolidol
- DMBA:
-
7, 1–2-Dimethylbenz (a) anthracene
- TNF-α:
-
Tumor necrosis factor-alpha
- NF-κB:
-
Nuclear factor kappa B
- COX-2:
-
Cyclooxygenase-2
- OSCC:
-
Oral squamous cell carcinoma
- RMSD:
-
Root mean square Deviation
- IHC:
-
Immunohistochemical
- SPSS:
-
Statistical Package for the Social Sciences
- PDB:
-
Protein data bank
- RMSF:
-
Root mean square Fluctuation
- MD:
-
Molecular dynamic simulation
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Acknowledgements
Indian Council of Medical Research (ICMR)] supported this study under [Grant No. 3/2/2/14/2020-NCD-III Dated: 24/12/2020], New Delhi, India, for providing financial support in the form of a Senior Research Fellowship to Miss. Vaitheeswari Balakrishnan.
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The experimental design got approval from the Institutional Animal ethics committee (IAEC) of Central animal house, Rajah Muthiah Medical College, Faculty of Medicine, Annamalai University (CPCSEA Registration No: 160/PO/ReBi/S/99/CPCSEA dated:25/11/19) (Proposal No: 1242, Dated:23.04.2019).
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Balakrishnan, V., Ganapathy, S., Veerasamy, V. et al. Modifying effects of nerolidol on cell surface glycoconjugates and suppressed inflammation during DMBA-induced oral carcinogenesis: An in vivo and in silico. Biologia 78, 529–541 (2023). https://doi.org/10.1007/s11756-022-01260-y
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DOI: https://doi.org/10.1007/s11756-022-01260-y