Banca de DEFESA: BARBARA FERNANDA PESSOA DE ANDRADE

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : BARBARA FERNANDA PESSOA DE ANDRADE
DATE: 28/02/2023
TIME: 14:00
LOCAL: Recife/PE
TITLE:

Determination of tumor cell death pathways of the mesoionic compound 2-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-5-thiolate (MI-2) in the Acute Promyelocytic Leukemia tumor cell line (HL-60)

KEY WORDS:

Antineoplastic, Heterocyclic betaines, Cancer, Cytotoxicity, Mechanism of Action

PAGES: 60
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUBÁREA: Clínica e Cirurgia Animal
SPECIALTY: Farmacologia e Terapêutica Animal
SUMMARY:

Cancer is a cosmopolitan disease, considered a public health issue, marked by deregulation of the cell cycle, which favors the proliferation of altered cells and the development of metastases from the migration of malignant cells to other regions of the body. According to the World Health Organization (WHO), cancer is among the leading causes of death worldwide. Thus, the search for new therapeutic possibilities that are effective and less toxic to patients has gained space in scientific research. The mesoionic family presents several heterocyclic chemical compounds with 5-atom rings and great structural variety. These compounds are essentially synthetic but may present naturally occurring rings in their chemical structures, according to each derivative, which may be oxazole, thiazole and thiadiazole. In addition, meosionics have been associated with numerous biological activities in the scientific community, including investigations into their antitumor potential in various cancer cell lines. Based on the positive results of mesoionics reported in the literature, the present study evaluated the antitumor potential and the main mechanisms of action in 72 hours of the derivative 2-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-5-thiolate (MI-2) in the Acute Promyelocytic Leukemia (HL-60) lineage. Viability tests were carried out in mononuclear cells (PBMC) and cellular cytotoxicity in HL-60, both by the MTT method; morphological analysis with HE staining and DNA analysis through the DNA ladder test. The results obtained indicated that MI-2 showed low cytotoxicity in rat lymphocytes (CEUA) and cytotoxicity for the HL-60 strain after 72h of treatment, with growth inhibition potential above 70% in the single dose test (25μg/mL) and dose of 2,03μg/mL for the calculation of the average Inhibitory Concentration (IC₅₀), according to the recommendations of the National Cancer Institute - USA (NCI) so that the compounds are considered promising for new experimental tests, the other tests of mechanism of action were performed at the same concentration. In the death mechanism analysis, the mesoionic derivative was able to induce death via apoptotic and autophagic pathways based on the observation of physiological events such as the formation of apoptotic bodies, nuclear fragmentation and the presence of autophagic vacuoles. These results indicate that the MI-2 compound has antitumor activity in HL-60 cells, however, further tests to deepen the mechanisms of action pathways are being carried out to confirm the anticancer potential of the MI-2.

COMMITTEE MEMBERS:
Presidente - EMMANUEL VIANA PONTUAL
Externa à Instituição - ELIZABETH FERNANDA DE OLIVEIRA BORBA - UFPE
Externo à Instituição - NATALY DINIZ DE LIMA SANTOS - UFRPE