NUMERO: #20230145

Título: NEW HISTONE MODIFICATION COMPOUNDS TO TREAT MUCOEPIDERMOID CARCINOMA IDENTIFIED BY HIGH THROUGHPUT SCREENING

Nome do Apresentador: Luan César da SILVA

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Oncologia

Resumo: Objective: Development of highly effective systemic strategies for MEC remains a challenge. In particular, there are few effective targeted therapies for MEC. In this way, high-throughput (HT) screening platforms have facilitated the rapid testing of many drugs. Here, we presented an HT drug screening by histone modification drugs (HMD) to pharmacologically assessed MEC and improve therapies.
Study design: High-precision-liquid-handler was used to seed UM-HMC3a cells and to administer drugs in a HT-format. MEC pharmacological assessment was conducted using a 2D-non cancer stem cells (CSC), and 3D-CSC models. Cell death was evaluated by propidium iodide in adherent cells and tumorspheres (CSC). ALDH levels and clonogenic potential were also investigated. All data were evaluated using ImageXpress from molecular devices.
Results: We identified 81 compounds inducing cell death in bulk MEC, and 92 compounds in CSC MEC. From this first HT screening, the top-drug candidates targeting each cell subpopulation was selected. After a careful validation process, we identified the final 4 compounds able to disrupt MEC. Additionally, ALDH levels were significantly reduced just for drugs selected based on CSC, while the clonogenic potential was reduced after the treatment with all selected drugs.
Conclusion: Administration of HMD can effectively target MEC and their stem cells.

Autor 1:  Luan César da SILVA

E-mail 1:  [email protected]

Autor 2:   Yeejin JANG

E-mail 2:  [email protected]

Autor 3 :  Pablo Agustin VARGAS

E-mail 3:  [email protected]

Autor 4:  Cristiane SQUARIZE

E-mail 4:  [email protected]

Autor 5:  Rogerio CASTILHO

E-mail 5:  [email protected]