Banca de DEFESA: DEBORA FROTA COLARES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : DEBORA FROTA COLARES
DATE: 28/08/2026
TIME: 14:00
LOCAL: AUDITÓRIO DO DEPARTAMENTO DE ODONTOLOGIA (HÍBRIDO) - NATAL - RN
TITLE:

Induction of Apoptosis by ABT-199 and Its Molecular Interactions in Oral Tongue Squamous Cell Carcinoma: An In Silico and In Vitro Study

KEY WORDS:

Keywords: Head and neck squamous cell carcinoma. Apoptosis regulation proteins. Antineoplastic protocols. Molecular targeted therapies.

PAGES: 83
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUBÁREA: Clínica Odontológica
SUMMARY:

Due to comorbidities and therapy resistance observed during conventional treatment of head and neck squamous cell carcinoma, targeted therapies serving as alternative or adjuvant to these treatments have been sought. ABT-199 (Venetoclax®️) is the first BH3-mimetic drug approved for clinical use in hematological malignancies, and it induces apoptosis in malignant cells through direct binding to Bcl-2. This study assessed the effects of ABT-199 on the proliferation and apoptosis in oral tongue squamous cell carcinoma (OTSCC) cells exhibiting high Bcl-2 expression, in order to understand its antineoplastic potential, as well as its influence on these cells. The affinity prediction between ABT-199 and the anti-apoptotic proteins Bcl-2, Bcl-xL, and MCL-1 was estimated through molecular docking. Viability and apoptosis assays were conducted in Cal27 and SCC-25 cell lines, whose effect of ABT-199 was evaluated at 1, 10, 50, 100, 500, and 1000 nM doses, alone or in combination with 5-FU (50 μM), and compared with the group treated only with 5-FU and the control group (PBS). Non-parametric tests were performed to verify differences between the analyzed groups, adopting a significance level of 5%. Bcl-2 showed the best binding energy (-11 kcal/mol), with emphasis on interactions with residues Asp111, Asp103, Asn143, and Tyr108. Cal27 and SCC-25, in descending order, exhibited the highest relative gene expression of Bcl-2. ABT-199 was able to reduce cell viability in OTSCC cells in a dose-dependent and time-dependent manner, with the combined therapy of 1µM with 5-FU being particularly noteworthy. Cal27 was more sensitive to these effects compared to the untreated group (p < 0.05). Pro-apoptotic effects of the combined therapy were identified when compared to the untreated groups in both cell lines (p < 0.05). Taken together, these findings indicate that ABT-199 appears to be a potential sensitizer of 5-FU-mediated cytotoxicity in OTSCC and suggest an alternative to chemoresistance to this drug in the treatment of OTSCC.

COMMITTEE MEMBERS:
Presidente - 1258707 - ANTONIO DE LISBOA LOPES COSTA
Interno - 2220417 - CARLOS AUGUSTO GALVAO BARBOZA
Interna - 350484 - ROSEANA DE ALMEIDA FREITAS
Externo à Instituição - EVERTON FREITAS DE MORAIS - UFC
Externa à Instituição - ROBERTA BARROSO CAVALCANTE - UNIFOR