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

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)