Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-β-cyclodextrin

Berta, Giovanni Nicolao; Salamone, Paolina; Sprio, Andrea Elio; Di Scipio, Federica; Marinos, Lucy Marcela; Sapino, Simona; Carlotti, Maria Eugenia; Cavalli, Roberta; Di Carlo, Francesco

doi:10.1016/j.oraloncology.2009.10.007

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Volume 46, Issue 1 , Pages 42-48, January 2010

Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-β-cyclodextrin

Giovanni Nicolao Berta
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy
- Corresponding author. Address: Department of Clinical and Biological Sciences, Ospedale San Luigi Gonzaga, I-10043 Orbassano, Italy. Tel.: +39 0116705446; fax: +39 0119038639.
- These authors contributed equally to this work.
Paolina Salamone
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy
- These authors contributed equally to this work.
Andrea Elio Sprio
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy
Federica Di Scipio
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy
Lucy Marcela Marinos
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy
Simona Sapino
- Department of Drug Science and Technology, University of Turin, I-10125 Torino, Italy
Maria Eugenia Carlotti
- Department of Drug Science and Technology, University of Turin, I-10125 Torino, Italy
Roberta Cavalli
- Department of Drug Science and Technology, University of Turin, I-10125 Torino, Italy
Francesco Di Carlo
- Department of Clinical and Biological Sciences, Pharmacology Unity, University of Turin, I-10043 Orbassano, Italy

Received 25 August 2009; received in revised form 21 October 2009; accepted 21 October 2009. published online 23 November 2009.

Summary

Oral squamous cell carcinoma (OSCC) develops slowly and it is usually preceded by identifiable oral preneoplastic lesions (OPLs): chemoprevention could be a promising approach. Resveratrol (RV) is a plant-based agent characterized by a strong in vitro antineoplastic action, but this effect has not been clinically confirmed owing to its metabolic inactivation. In order to circumvent this limitation and to improve RV efficacy, it was locally applied and complexed with a protective and solubilising vehicle (2-hydroxypropyl-β-cyclodextrin, HPβCD). The experimentation was performed in vitro on 7,12-dimethylbenz[a]anthracene-induced hamster OSCC cell line (HCPC I) and in vivo in the related animal model, by comparison of two RV–HPβCD formulations (cream and mouthwash) and RV alone. Vehicles and RV-formulations were free from toxicity. Antiproliferative action of RV on HCPC I was concentration- and time-dependent, and was improved in HPβCD-formulations. In vivo, RV prevented OPL and OSCC appearance and growth. Here, too, HPβCD-formulations (mainly mouthwash) demonstrated the best chemopreventive effects in terms of lesions prevalence, multiplicity, dimension, and histological signs of malignancy. HPLC detection of RV corroborated that its action is concentration-correlated and is improved by its inclusion in HPβCDs. In summary, our study demonstrates that RV is effective in the chemoprevention of DMBA-induced oral carcinogenesis and when it is complexed with HPβCDs its efficacy is significantly improved.

Keywords: Oral cancer, Preneoplastic lesions, Resveratrol, Cyclodextrins, Chemoprevention, Hamster cheek pouch model, DMBA