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Oncol Rep. 2018 Sep;40(3):1435-1442. doi: 10.3892/or.2018.6555. Epub 2018 Jul 10.

Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study.

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Department of Veterinary Medicine and Animal Production, University Federico II of Naples, I-80137 Naples, Italy.
Department of Biochemical, Biophysical and General Pathology, Università della Campania 'Luigi Vanvitelli', I-80138 Naples, Italy.
CNR‑ISA National Research Council, Institute of Food Science, I-83100 Avellino, Italy.
Ministry of Education, University and Research (MIUR); CPIA Naples City 1, Pasquale Scura' Polo Tecnico Fermi Gadda, I‑80141 Naples, Italy.
Department of Veterinary Medicine and Animal Production, University Federico II of Naples, I-80137 Naples, Italy.
Department of Clinical Sciences, Polytechnic University of Marche, I-60121 Ancona, Italy.
Glures spin‑off CNR‑IFT National Research Council, Translational Institute of Pharmacology, I‑00133 Rome, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy.


Oral squamous cell carcinoma (OSCC) is one of the most aggressive and deadliest tumors worldwide. The aryl hydrocarbon receptor (AHR) is a nuclear transcription factor known as a dioxin receptor and mediates the toxic effects of industrial contaminants. In addition, AHR has been implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis, including human oral cancer cell lines. In the present study, we evaluated the expression of AHR/HSP-90 in 25 formalin‑fixed, paraffin-embedded human oral cancer specimens by IHC analysis. CYP1A1 expression was regarded as an AHR reporter gene. The data indicated a complete correlation between AHR expression and cancer grade enabling us to propose AHR as a prognostic marker of oral cancer. Moreover, in OSCC cell line CAL27, we observed the modulatory effect of polydatin, a widespread natural substance and direct precursor of resveratrol, on AHR expression. A computational approach was performed to predict the site of interaction of polydatin on the AHR surface. Our studies confirm the involvement of AHR signaling in the clinicopathological specimens of oral cancer and suggest the use of polydatin for oral cancer prevention.

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