Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.
Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.
['Bonfim|Caroline Measso do|CMD|', 'Monteleoni|Letícia Figueiredo|LF|', 'Calmon|Marília de Freitas|MF|', 'Cândido|Natália Maria|NM|', 'Provazzi|Paola Jocelan Scarin|PJS|', 'Lino|Vanesca de Souza|VS|', 'Rabachini|Tatiana|T|', 'Sichero|Laura|L|', 'Villa|Luisa Lina|LL|', 'Quintana|Silvana Maria|SM|', 'Melli|Patrícia Pereira Dos Santos|PPDS|', 'Primo|Fernando Lucas|FL|', 'Amantino|Camila Fernanda|CF|', 'Tedesco|Antonio Claudio|AC|', 'Boccardo|Enrique|E|', 'Rahal|Paula|P|']
D000328:Adult D000998:Antiviral Agents D002278:Carcinoma in Situ D045744:Cell Line, Tumor D002470:Cell Survival D003474:Curcumin D004655:Emulsions D005260:Female D005838:Genotype D052162:Human papillomavirus 16 D006801:Humans D008027:Light D053758:Nanoparticles D009856:Oncogene Proteins, Viral D030361:Papillomavirus Infections D017319:Photosensitizing Agents D012097:Repressor Proteins D014846:Vulvar Neoplasms
Vulvar intraepithelial neoplasia HPV nanoemulsion curcumin and photodynamic therapy