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| Author(s): |
Ana Beatriz Bortolozo de Oliveira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São José do Rio Preto. 2016-03-10. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto |
| Defense date: | 2016-03-01 |
| Advisor: | Paula Rahal; Marilia de Freitas Calmon; Luis Octávio Regasini |
| Abstract | |
High risk Human Papilomavírus (HPVs) are DNA vírus divided in two groups. Low risk, associated with benign lesions, and high risk, associated with several types of cancer. Oncoproteins HPV E6 and E7 are the main proteins involved in the carcinogenesis process due to infection by this virus, so that natural coumponds have been used in the search for drugs that inhibit viral expression. At the same time, due to various side effects and high relapse rate of traditional cancer treatments, the search for antitumor agents is intense. In this context, several studies are being conducted in order to explore the numerous properties of curcumin, a substance that has anti-inflammatory, immune-modulatory, anti-oxidant, anti-angiogenic, chemoprotective, anti-proliferative, anti-tumor and anti-microbial properties. Thus, a promising strategy used is the search for curcumin analogues which are able to increase the therapeutic efficacy of phytotherapy. Thus, the aim of this study is to analyze the action of different semi-synthetic derivatives of curcumin (AC1, AC2, AC7, AC10 and AC13) on the E6 and E7 viral oncogenes expression in positive HPV-16 cervical carcinoma cell line (CasKi) and the antitumor activity of AC13 compound in different tumor cell lines (CasKi, HeLa, MDA 231, MCF-7 and 786-O). For this, after incubation with the compounds at different concentrations, cell viability was analyzed by MTT assay and a spontaneously transformed immortal keratinocyte cell line (HaCaT) was used as a control to analyze the cytotoxicity. Subsequently, E6 and E7 mRNA expression evaluation was performed by real-time PCR, p53 protein expression determination was analyzed by Western Blotting, and detecting the caspases 3 and 7 activity was analyzed using the luminescent assay of apoptosis. Although no compound has inhibited E6 and E7 expression in the CasKi cell line, AC13 cytotoxicity analyzes suggest that it has advantages in relation to curcumin in this cell line, because it was more cytotoxic than curcumin to no tumoral cells (HaCaT) and caused viability decrease less pronunced for CasKi line than for HaCaT at 50, 75 e 100 μM. Furthermore, AC13 induces increased caspases activity, suggesting cell death by apoptosis. Thus, our datas suggest that AC13 derivative of curcumin presents interesting antitumor activity in CasKi cells. (AU) | |
| FAPESP's process: | 14/04395-2 - In vitro action of semi-synthetic curcumin derivatives on high-risk HPV E6 oncogene expression |
| Grantee: | Ana Beatriz Bortolozo de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Master |