NUMERO: #20231031

Título: HIGH-THROUGHPUT SCREENING WITH EPIGENETIC DRUGS AIMING TO REDUCE MIGRATION AND INVASION OF ADENOID CYSTIC CARCINOMA

Nome do Apresentador: Paulo Sergio Souza PINA

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Patologia Oral

Resumo: Objective: Our objective was to tackle the current lack of effective drugs capable of manage ACC progression, by identifying new drugs, through a high-throughput screening of epigenetic drugs, that prevent epithelial-mesenchyme transition (EMT) and disrupt cancer stem-cells (CSCs).
Study Design: UM-ACC-2A cell line was seeded using a robotic liquid handler system (Opentrons) and cultured in two 96-well plates. Changes in cell viability and morphology were analyzed 24 hrs after adding drugs using a high-content imaging system (ImageXpress). Aiming at changes associated with EMT, we used snail antibody while using H3K9 as indicative of epigenetic modifications. Those drugs identified as of clinical interest were validated by assays that determined cellular toxicity index, flow of snail, the ability to reduce cell migration and the capacity of interrupt tumor spheres.
Results: Seven compounds showing favorable levels of toxicity and capable of reducing cell viability, inhibiting snail expression, inducing histone acetylation, and interrupting CSCs were identified. The validation assays showed that the drugs Scriptaid and LMK235 presented the most promising results to open new ways for the treatment of salivary gland ACC.
Conclusion: We have identified novel drugs that hold the promise for new therapeutic strategies to manage ACC tumors from the salivary glands.

Autor 1:  Paulo Sergio Souza PINA

E-mail 1:  [email protected]

Autor 2:   Yeejin JANG

E-mail 2:  [email protected]

Autor 3 :  João Figueira SCARINI

E-mail 3:  [email protected]

Autor 4:  Carolina EMERICK

E-mail 4:  [email protected]

Autor 5:  Suzana Cantanhede Orsini Machado de SOUSA

E-mail 5:  [email protected]

Autor 6:  Cristiane Helena SQUARIZE

E-mail 6:  [email protected]

Autor 7:  Rogério Moraes CASTILHO

E-mail 7:  [email protected]