Banca de DEFESA: ANA CLÁUDIA DE MACEDO ANDRADE

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANA CLÁUDIA DE MACEDO ANDRADE
DATE: 31/03/2022
TIME: 14:00
LOCAL: PLATAFORMA REMOTA
TITLE:

IN VITRO AND IN SILICO EVALUATION OF THE ANTINEOPLASTIC ACTIVITY OF S-(-)-PERILLYL ALCOHOL ON EQUAMOUS CELL CARCINOMA OF THE TONGUE

KEY WORDS:

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

PAGES: 111
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

Oral squamous cell carcinoma (OSCC) is the most frequent malignant neoplasm of the oral cavity and constitutes a public health problem due to its high incidence and mortality rate caused in many cases by therapeutic failure and tumor resistance. Therefore, the search for new biologically active molecules stands out, such as those found in products of natural origin. This work aims to evaluate the antineoplastic activity of S-(-)-perillyl alcohol (POH) in cell cultures of tongue CEO and to analyze the probable mechanism of action on the antineoplastic activity of this phytoconstituent through molecular docking. For this purpose, two cell lines of tongue CEO were used, HSC-3 and SCC-25. The following groups were analyzed: G0 (control; cells cultured 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 .0 mM), G4 (cells treated with 1.5 mM POH) and G5 (cells treated with 3.0 mM POH). Differences between these groups were investigated through the following assays: cell viability (Alamar Blue and Live/Dead assay) and migratory activity (Wound healing). The prediction of the POH action mechanism on cell cycle control molecules were also performed using molecular docking using AutoDock 4.2 and Molegro Virtual Docker, v. 6.0.1. The data was statistically treated by GraphPad Prism 6.0 (GraphPad Software, USA), parametric analysis using Anova test, Tukey post-test and Kruskal-Wallis non-parametric statistical test, followed by Mann-Whitney post-test were adopted for determination of differences between the experimental groups. The significance index considered in this work was 5%. In the analysis of cell viability using Alamar Blue, for the cell line SCC-25, cell viability was significantly reduced in the 40 μM cisplatin, 0.5 mM POH, 1 mM POH, 1.5 mM POH and 3 mM POH groups (p<0.05), at intervals of 24 h and 48 h when compared to the growth control. In turn, in the 72 h interval, only the 0.5 mM POH concentration showed no statistical difference when compared to the control group (p= 0.35). For the HSC-3 cell line, there was a significant decrease in viability in the 40 μM, 1 mM, 1.5 mM and 3 mM cisplatin groups (p<0.01), in the time interval of 24h, 48h and 72h, when compared to growth control. Furthermore, for both strains, the 3 mM POH concentration presented the best results of viability reduction when compared to 40 μM cisplatin, in the intervals of 24 h for SCC-25 and 24 h (p<0.01) and 48h (p<0.01) for HSC-3. In the analysis of cell viability by the Live/Dead assay, for the cell line SCC-25, all experimental groups showed a significant reduction in the percentage of cell viability (p<0.001) when compared to the control group, since, for the HSC line -3, only the 0.5 mM POH group showed no statistically significant difference compared to the control group (p= 0.9663). As for the anti-migratory capacity of POH, for the SCC-25 strain, the 40 μM cisplatin, 0.5 mM POH and 1.0 mM POH groups had a statistically significant reduction in cell migration when compared to the control group, at 12 h, on the other hand, within 24 h, only cisplatin showed anti-migratory activity (p≤ 0.05). For the HSC-3 strain, the 40 μM cisplatin and 1 mM POH groups showed statistical differences compared to the control group (p≤ 0.05), at 12 h and 24 h intervals. The ability of the POH molecule to bind to proteins responsible for cell cycle activation was evaluated using docking models. Among them, the protein GTPase Kras showed the best binding energy (-86.70 kcal/mol), featuring hydrogen bonds with residues THR58 (A) and ASP57 (A) and steric bonds with residues TRY32 (A) and ALA18 ( THE). The evidence from this study supports the idea that POH has antineoplastic activity on the CEO, suggesting that this molecule may be a strong candidate for the development of drugs aimed at the treatment of this pathology.

BANKING MEMBERS:
Externa à Instituição - LUCIANA SCOTTI - UFPB
Presidente - 1258707 - ANTONIO DE LISBOA LOPES COSTA
Interna - 2374605 - AURIGENA ANTUNES DE ARAUJO
Interno - 2220417 - CARLOS AUGUSTO GALVAO BARBOZA
Externa à Instituição - SABRINA GARCIA DE AQUINO - UFPB