In vitro action of semi-synthetic curcumin derivatives on high-risk HPV E6 oncogene expression

• Grant number: 14/04395-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2014
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Paula Rahal
• Grantee: Ana Beatriz Bortolozo de Oliveira
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The Human Papillomaviruses (HPVs) are DNA viruses belonging to the family Papillomaviridae. HPVs with tropism for mucosal tissue are divided into two groups, low and high oncogenic risk, low risk lead to the development of benign intraepithelial lesions, while high-risk HPVs are associated with genital and head and neck cancers. However, the main tumor type related to HPV is cervical cancer, being found viral DNA in over 96% of cases. The E6 oncoprotein of high risk HPV is a key protein involved in the carcinogenesis process due to the infection. E6 binds and degrades p53 protein, preventing the infected cell to apoptosis, which contributes to uncontrolled cell proliferation. The traditional treatments for HPV involve surgery, chemotherapy and radiotherapy. However, these treatments cause side effects and recurrence is common. Thus, natural compounds have been used in the search for drugs which inhibit viral expression. In this context, researches are conducted to cancer treatment with curcumin, a substance that has anti-inflammatory, immuno-modulatory, anti-angiogenic and anti-proliferative, antimicrobial and antioxidant properties. This phytotherapic decreases the level of E6 mRNA and restores the level of p53 protein in HPV-positive cervical carcinoma cells lines. However, curcumin exhibits low bioavailability and rapid metabolism and excretion. A promising strategy to overcome these obstacles is the search for synthetic curcumin derivatives that increase the therapeutic efficacy of these phytotherapic. The aim of this study is to analyze, in vitro, the action of different semi- synthetic curcumin derivatives on the expression of the HPV 16 E6 viral oncogene and on your target gene (p53) expression in HPV 16 positives cell lines. For this, the viability of cells incubated with the compounds at different concentrations will be analyzed by MTT assay. The evaluation of the mRNA expression of E6 and p53 will be performed by qPCR and determination of p53 protein expression will be obtained by Western blotting. Thus, this work will be able to demonstrate which semi-synthetic curcumin derivative shows better efficacy to inhibit p53 protein degradation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BORTOLOZO OLIVEIRA, ANA BEATRIZ; ADUM DE MATOS, RENATA PRANDINI; STUQUI, BRUNA; TORREZAN, GUILHERME SILVA; POLAQUINI, CARLOS ROBERTO; REGASINI, LUIS OCTAVIO; CALMON, MARILIA DE FREITAS; RAHAL, PAULA. Cytotoxicity and Antitumoral Activity by Apoptosis Induction of AC13: A Brominated Curcumin Analogue. PHARMACOGNOSY MAGAZINE, v. 14, n. 58, p. 611-616, OCT-DEC 2018. (14/04395-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OLIVEIRA, Ana Beatriz Bortolozo de. Study of curcumin semisynthetic derivatives action in cell lines of human cancer. 2016. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.