Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-beta-cyclodextrin.
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-beta-cyclodextrin, HPbetaCD). 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-HPbetaCD 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 HPbetaCD-formulations. In vivo, RV prevented OPL and OSCC appearance and growth. Here, too, HPbetaCD-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 HPbetaCDs. In summary, our study demonstrates that RV is effective in the chemoprevention of DMBA-induced oral carcinogenesis and when it is complexed with HPbetaCDs its efficacy is significantly improved.
Berta
Giovanni Nicolao
GN
Department of Clinical and Biological Sciences, University of Turin, I-10043 Orbassano, Italy.giovanni.berta@unito.it
Salamone
Paolina
P
Sprio
Andrea Elio
AE
Di Scipio
Federica
F
Marinos
Lucy Marcela
LM
Sapino
Simona
S
Carlotti
Maria Eugenia
ME
Cavalli
Roberta
R
Di Carlo
Francesco
F
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015127:9,10-Dimethyl-1,2-benzanthracene; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002610:Cheek; D006224:Cricetinae; D004338:Drug Combinations; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004338:Drug Combinations; D014677:Pharmaceutical Vehicles; D013267:Stilbenes; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015127:9,10-Dimethyl-1,2-benzanthracene; D000077185:Resveratrol