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

Martano,Manuela; Stiuso,Paola; Facchiano,Angelo; De Maria,Salvatore; Vanacore,Daniela; Restucci,Brunella; Rubini,Corrado; Caraglia,Michele; Ravagnan,Giampietro; Lo Muzio,Lorenzo

doi:10.3892/or.2018.6555

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

Authors:
- Manuela Martano
- Paola Stiuso
- Angelo Facchiano
- Salvatore De Maria
- Daniela Vanacore
- Brunella Restucci
- Corrado Rubini
- Michele Caraglia
- Giampietro Ravagnan
- Lorenzo Lo Muzio
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Affiliations: 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
Published online on: July 10, 2018 https://doi.org/10.3892/or.2018.6555
Pages: 1435-1442

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Abstract

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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1	Poland A, Palen D and Glover E: Tumour promotion by TCDD in skin of HRS/J hairless mice. Nature. 300:271–273. 1982. View Article : Google Scholar : PubMed/NCBI
2	Murray IA, Patterson AD and Perdew GH: Aryl hydrocarbon receptor ligands in cancer: Friend and foe. Nat Rev Cancer. 14:801–814. 2014. View Article : Google Scholar : PubMed/NCBI
3	Meyer BK, Pray-Grant MG, Vanden Heuvel JP and Perdew GH: Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Mol Cell Biol. 18:978–88. 1998. View Article : Google Scholar : PubMed/NCBI
4	Zhou S, Liu J and Chowbay B: Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 41:89–295. 2009. View Article : Google Scholar : PubMed/NCBI
5	Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, et al: Role for the Aryl hydrocarbon receptor and diverse ligands in oral squamous cell carcinoma migration and tumorigenesis. Mol Cancer Res. 14:696–706. 2016. View Article : Google Scholar : PubMed/NCBI
6	Quattrochi LC and Tukey RH: Nuclear uptake of the Ah (dioxin) receptor in response to omeprazole: Transcriptional activation of the human CYP1A1 gene. Mol Pharmacol. 43:504–508. 1993.PubMed/NCBI
7	Singh SU, Casper RF, Fritz PC, Sukhu B, Ganss B, Girard B Jr, Savouret JF and Tenenbaum HC: Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol. J Endocrinol. 167:183–195. 2000. View Article : Google Scholar : PubMed/NCBI
8	Lee JE and Safe S: Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells. Biochem Pharmacol. 62:1113–1124. 2001. View Article : Google Scholar : PubMed/NCBI
9	He H, Zhao Y, Chen X, Zheng Y, Wu X, Wang R, Li T, Yu Q, Jing J, Ma L, et al: Quantitative determination of trans-polydatin, a natural strong anti-oxidative compound, in rat plasma and cellular environment of a human colon adenocarcinoma cell line for pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 855:145–151. 2007. View Article : Google Scholar : PubMed/NCBI
10	Henry-Vitrac C, Desmoulière A, Girard D, Mérillon JM and Krisa S: Transport, deglycosylation, and metabolism of trans-piceid by small intestinal epithelial cells. Eur J Nutr. 45:376–382. 2006. View Article : Google Scholar : PubMed/NCBI
11	Rotches-Ribalta M, Andres-Lacueva C, Estruch R, Escribano E and Urpi-Sarda M: Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacol Res. 66:375–382. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ravagnan GP: Extracts from spermatophyte plants with antitumor activity Euoropean Patent EP1292319B1. Filed May 29, 2001; issued Aug 15. 2002
13	Wang C, Luo Y, Lu J, Wang Y and Sheng G: Polydatin induces apoptosis and inhibits growth of acute monocytic leukemia cells. J Biochem Mol Toxicol. 30:200–205. 2016. View Article : Google Scholar : PubMed/NCBI
14	Cao WJ, Wu K, Wang C and Wan DM: Polydatin-induced cell apoptosis and cell cycle arrest are potentiated by Janus kinase 2 inhibition in leukemia cells. Mol Med Rep. 13:3297–3302. 2016. View Article : Google Scholar : PubMed/NCBI
15	Zhang Y, Zhuang Z, Meng Q, Jiao Y, Xu J and Fan S: Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest. Oncol Lett. 7:295–301. 2014. View Article : Google Scholar : PubMed/NCBI
16	De Maria S, Scognamiglio I, Lombardi A, Amodio N, Caraglia M, Cartenì M, Ravagnan G and Stiuso P: Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell. J Transl Med. 11:2642013. View Article : Google Scholar : PubMed/NCBI
17	Hogg SJ, Chitcholtan K, Hassan W, Sykes PH and Garrill A: Resveratrol, acetyl-resveratrol, and polydatin exhibit antigrowth activity against 3D cell aggregates of the SKOV-3 and OVCAR-8 ovarian cancer cell lines. Obstet Gynecol Int. 2015:2795912015. View Article : Google Scholar : PubMed/NCBI
18	Hughes D, Guttenplan JB, Marcus CB, Subbaramaiah K and Dannenberg AJ: Heat shock protein 90 inhibitors suppress aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and DNA adduct formation. Cancer Prev Res. 1:485–493. 2008. View Article : Google Scholar
19	Tsuji N, Fukuda N, Nagata Y, Okada H, Haga A, Hatakeyama S, Yoshida S, Okamoto T, Hosaka M, Sekine K, et al: The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP-90. FEBS Open Bio. 4:796–803. 2014. View Article : Google Scholar : PubMed/NCBI
20	Salzano M, Marabotti A, Milanesi L and Facchiano A: Human aryl-hydrocarbon receptor and its interaction with dioxin and physiological ligands investigated by molecular modelling and docking simulations. Biochem Biophys Res Commun. 413:176–181. 2011. View Article : Google Scholar : PubMed/NCBI
21	Bryne M, Koppang HS, Lilleng R, Stene T, Bang G and Dabelsteen E: New malignancy grading is a better prognostic indicator than Broder's grading in oral squamous cell carcinomas. J Oral Pathol Med. 18:432–437. 1989. View Article : Google Scholar : PubMed/NCBI
22	Martano M, Carella F, Squillacioti C, Restucci B, Mazzotta M, Lo Muzio L and Maiolino P: Metallothionein expression in canine cutaneous apocrine gland tumors. Anticancer Res. 32:747–752. 2012.PubMed/NCBI
23	John K, Lahoti TS, Wagner K, Hughes JM and Perdew GH: The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines. Mol Carcinog. 53:765–76. 2014. View Article : Google Scholar : PubMed/NCBI
24	DiNatale BC, Smith K, John K, Krishnegowda G, Amin SG and Perdew GH: Ah receptor antagonism represses head and neck tumor cell aggressive phenotype. Mol Cancer Res. 10:1369–1379. 2012. View Article : Google Scholar : PubMed/NCBI
25	Yin XF, Chen J, Mao W, Wang YH and Chen MH: Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion. Oncol Rep. 30:364–370. 2013. View Article : Google Scholar : PubMed/NCBI
26	Tsai CH, Li CH, Cheng YW, Lee CC, Liao PL, Lin CH, Huang SH and Kang JJ: The inhibition of lung cancer cell migration by AhR-regulated autophagy. Sci Rep. 7:419272017. View Article : Google Scholar : PubMed/NCBI
27	Brooks J and Eltom SE: Malignant transformation of mammary epithelial cells by ectopic overexpression of the aryl hydrocarbon receptor. Curr Cancer Drug Targets. 11:654–669. 2011. View Article : Google Scholar : PubMed/NCBI
28	Al-Dhfyan A, Alhoshani A and Korashy HM: Aryl hydrocarbon receptor/Cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation. Mol Cancer. 16:692017. View Article : Google Scholar : PubMed/NCBI
29	Androutsopoulos VP, Tsatsakis AM and Spandidos DA: Cytochrome P450 CYP1A1: Wider roles Androutsopoulos in cancer progression and prevention. BMC Cancer. 9:1872009. View Article : Google Scholar : PubMed/NCBI
30	Moyer BJ, Rojas IY, Murray IA, Lee S, Hazlett HF, Perdew GH and Tomlinson CR: Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor. Toxicol Appl Pharmacol. 323:74–80. 2017. View Article : Google Scholar : PubMed/NCBI
31	Hamidullah, Kumar R, Saini KS, Kumar A, Kumar S, Ramakrishna E, Maurya R, Konwar R and Chattopadhyay N: Quercetin-6-C-β-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor. Biochimie. 119:68–79. 2015. View Article : Google Scholar : PubMed/NCBI
32	Chang CH, Lee CY, Lu CC, Tsai FJ, Hsu YM, Tsao JW, Juan YN, Chiu HY, Yang JS and Wang CC: Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. Int J Oncol. 50:873–882. 2017. View Article : Google Scholar : PubMed/NCBI