Estudo da ação de nanopartículas associadas à curcumina em células de carcinoma cervical positivo para HPV-16
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Data
2017-03-02
Autores
Matos, Renata Prandini Adum de [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Os Papilomavírus Humanos (HPV) são uma família de vírus de DNA com mais de 202 tipos, e são divididos em HPVs de alto e baixo risco. A infecção pelo HPV de alto risco foi identificada como agente etiológico de seis tipo de câncer, incluindo o carcinoma de colo de útero, de pênis, vagina, vulva, ânus e orofaringe, sendo que em aproximadamente 99,7 % dos casos de câncer cervical a infecção pelo HPV de alto risco é relacionado como agente etiológico. O tratamento atual para carcinoma invasivo é a terapia combinada do quimioterápico cisplatina com a radiação, contudo a cisplatina apresenta sérios efeitos adversos. Assim, é de extrema importância o desenvolvimento de novas estratégias terapêuticas, que aumentem a eficácia do quimioterápico e diminua os efeitos colaterais, a fim de maximizar a resposta local e promover a sobrevida do paciente. A curcumina é um composto hidrofóbico bioativo muito versátil que possui propriedades antioxidante, anti-inflamatória, anti-hiperlipidêmica, antiangiogênica, antineoplásica e quimioprotetora. Além disso, a curcumina pode ser usada como agente fotossensível na Terapia Fotodinâmica. Entretanto, sua aplicação como agente ativo tem sido limitada pela sua baixa solubilidade em água e biodisponibilidade. Assim, este trabalho teve como objetivo avaliar os efeitos da Terapia Fotodinâmica na viabilidade celular usando nanoemulsões com curcumina, como fármaco fotossensibilizante, em linhagens de carcinoma cervical HPV-16 positivas cultivadas em monocultura. A ausência de citotoxicidade de nanoemulsões vazias demonstra sua biocompatibilidade. Adicionalmente, o tratamento com nanoemulsões com curcumina na concentração de 20 μM de curcumina possui mais de 80% de viabilidade celular para todas as linhagens celulares analisadas. As nanoemulsões foram capazes de se internalizarem eficientemente nas células analisadas, sendo observadas intracelularmente por até 36 horas nas células SiHa e por até 48 horas nas células CasKi e HaCat. Após o tratamento com a Terapia Fotodinâmica, observou-se alto efeito fototóxico das nanoemulsões com curcumina, sendo observado menos de 5% de viabilidade celular após a irradiação. Esse efeito foi acompanhado por um aumento na atividade das caspases 3/7, sugerindo morte celular por apoptose. Assim é possível concluir que a formulação de nanoemulsão com curcumina como agente fotossensível para a Terapia Fotodinâmica mostra potencial como terapia alternativa para carcinoma cervical.
The Human Papillomavirus (HPV) is a family of DNA viruses with more than 202 types, and are divided into high and low risk HPVs. High-risk HPV infection was identified as etiologic agent of six types of cancer, including cancer of the cervix, penis, vagina, vulva, anus, and oropharynx, and, approximately, 99.7% of the cases of cervical cancer are caused by high-risk HPV infections. Current treatment modalities for invasive carcinoma are the combination of cisplatinbased chemotherapy with radiation, however cisplatin shows severe adverse effects and a low survival rate. Therefore, ongoing efforts are necessary to developed news effective therapeutic strategies to enhance chemotherapeutic efficacy and decrease these side effects, maximizing the local response and patient survival. Curcumin is a bioactive versatile hydrophobic compound which has anti-inflammatory, anti-hyperlipidaemic, anti-angiogenic, anti-neoplastic and chemoprotective properties. Furthermore, curcumin may be used as a photosensitizing agent in Photodynamic Therapy. This study aimed to investigate the effects of Photodynamic Therapy in cellular viability using curcumin-nanoemulsion as photosensitizing drug in cervical carcinoma HPV- 16 cell lines and identify possible molecular changes. The absence of cytotoxicity of empty nanoemulsion showed its biocompatibility. Additionally, the incubation with curcumin-nanoemulsion at 20 μM of curcumin showed more than 80% of cell viability for cell lines. Nanoemulsions were internalized efficiently in cells and were observed in the intracellular environment for up 36 hours after incubation in SiHa cells and for 48 hours in CasKi cells by fluorescence microscopy. Besides, after the Photodynamic Therapy we observed high phototoxic effect of the curcumin-nanoemulsion with less than 5% of viable cells after irradiation. This was accompanied by an increase in caspase-3/7, suggesting cell death by apoptosis. We conclude that curcuminnanoemulsion formulation behaves as photosensitizing agent in Photodynamic Therapy and shows potential as an alternative treatment to cervical carcinoma.
The Human Papillomavirus (HPV) is a family of DNA viruses with more than 202 types, and are divided into high and low risk HPVs. High-risk HPV infection was identified as etiologic agent of six types of cancer, including cancer of the cervix, penis, vagina, vulva, anus, and oropharynx, and, approximately, 99.7% of the cases of cervical cancer are caused by high-risk HPV infections. Current treatment modalities for invasive carcinoma are the combination of cisplatinbased chemotherapy with radiation, however cisplatin shows severe adverse effects and a low survival rate. Therefore, ongoing efforts are necessary to developed news effective therapeutic strategies to enhance chemotherapeutic efficacy and decrease these side effects, maximizing the local response and patient survival. Curcumin is a bioactive versatile hydrophobic compound which has anti-inflammatory, anti-hyperlipidaemic, anti-angiogenic, anti-neoplastic and chemoprotective properties. Furthermore, curcumin may be used as a photosensitizing agent in Photodynamic Therapy. This study aimed to investigate the effects of Photodynamic Therapy in cellular viability using curcumin-nanoemulsion as photosensitizing drug in cervical carcinoma HPV- 16 cell lines and identify possible molecular changes. The absence of cytotoxicity of empty nanoemulsion showed its biocompatibility. Additionally, the incubation with curcumin-nanoemulsion at 20 μM of curcumin showed more than 80% of cell viability for cell lines. Nanoemulsions were internalized efficiently in cells and were observed in the intracellular environment for up 36 hours after incubation in SiHa cells and for 48 hours in CasKi cells by fluorescence microscopy. Besides, after the Photodynamic Therapy we observed high phototoxic effect of the curcumin-nanoemulsion with less than 5% of viable cells after irradiation. This was accompanied by an increase in caspase-3/7, suggesting cell death by apoptosis. We conclude that curcuminnanoemulsion formulation behaves as photosensitizing agent in Photodynamic Therapy and shows potential as an alternative treatment to cervical carcinoma.
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Palavras-chave
Nanotecnologia, Carcinoma cervical, Curcumina, HPV