Banca de QUALIFICAÇÃO: ANA CLÁUDIA DE MACEDO ANDRADE

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANA CLÁUDIA DE MACEDO ANDRADE
DATE: 20/12/2021
TIME: 08:30
LOCAL: Online
TITLE:

Evaluation of the antineoplastic activity of S-(-)-perillyl alcohol on tongue squamous cell carcinoma

KEY WORDS:

Squamous Cell Carcinoma of Head and Neck; Monoterpenes; Antineoplastic Agents; Computer Simulation.

PAGES: 58
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

Introduction: Oral squamous cell carcinoma (OSC) is the most frequent malignant neoplasm of the oral cavity and is a public health problem due to its high incidence and mortality rate. The treatment of this neoplasm is based on the surgical removal of the lesion and/or the use of chemotherapy and radiotherapy. Regarding the use of chemotherapy drugs, a limited number are currently available on the market, they are drugs that cause several side effects, in addition to the possibility of reducing their effectiveness due to increased resistance by neoplastic cells. Therefore, the search for products of natural origin stands out, including essential oils and their constituents. Objective: This work aims to evaluate the antineoplastic activity of S-(-)-perillyl alcohol (POH) in tongue cell cultures and to evaluate the likely mechanism of action of this phytoconstituent through the analysis by computational docking model. Methodology: Two tongue OSC cell lines will be used, HSC-3 and SCC-25. The following groups will be analyzed: G0 (control; cells grown in the absence of POH), G1 (cells treated with 40 μM cisplatin), G2 (cells treated with 0.5 mM POH), G3 (cells treated with 1 POH ), 0 mM) G4 (cells treated with 1.5 mM POH) G5 (cells treated with 3.0 mM POH). Differences between the groups will be investigated through the following assays: cell viability (Alamar Blue, Live / Dead, LDH enzyme), cell cycle (labeled with propidium iodide, PI), apoptosis/necrosis (labeled with Annexin V and PI), migratory activity (Wound healing) and cell invasion (Transwell). It will also be performed a prediction of the mechanism of action of POH on cell cycle control molecules using molecular docking with the software AutoDock 4.2 and Molegro Virtual Docker, v. 6.0.1. An exploratory analysis of the data will be performed to determine the most appropriate statistical approach for each trial. The data will be statistically treated by GraphPad Prism 6.0 (GraphPad Software, USA), with a significance level of 5%. Partial Results: In the analysis of cell viability using Alamar Blue, for the SCC-25 cell line, the cell viability was significantly reduced in the groups 40μM cisplatin (p<0.05), 0.5mM POH (p<0.05), POH 1mM (p<0.05), POH 1.5mM (p <0.05) and POH 3mM (p<0.05), in the intervals of 24h and 48h, when compared to the growth control. On the other hand, in the interval of 72h, only the 0.5mM POH concentration did not present a statistical difference when compared to the control group (p= 0.3481). For the HSC-3 cell line, there was a decreasing decrease in viability in the 40μM (p<0.01), 1 mM (p< 0.01), 1.5 mM (p<0.01) and 3 mM (p<0.01) cisplatin groups. 0.0) in the time interval of 24h, 48h, and 72h when compared to the growth control. In addition, for both strains, the 3mM POH concentration showed better results in terms of reduced viability when compared to 40μM cisplatin in the 24h intervals for SCC-25 (p<0.01) and 24h (p<0.01) and 48h (p<0.01) for HSC-3. The ability of the POH molecule to bind to the proteins responsible for cell cycle activation was evaluated using docking models. Among them, the GTPase Kras protein showed the highest binding energy with the POH molecule, featuring hydrogen bonds with THR58 (A) and ASP57 (A) residues and steric bonds with TRY32 (A) and ALA18 (A) residues.

BANKING MEMBERS:
Presidente - 1258707 - ANTONIO DE LISBOA LOPES COSTA
Interna - 2374605 - AURIGENA ANTUNES DE ARAUJO
Interno - 2220417 - CARLOS AUGUSTO GALVAO BARBOZA