| Autor: |
da SILVA, Luan César, JANG, Yeejin, VARGAS, Pablo Agustin, SQUARIZE, Cristiane, CASTILHO, Rogerio |
| Zdroj: |
Oral Surgery, Oral Medicine, Oral Pathology & Oral Radiology; Jun2024, Vol. 137 Issue 6, pe276-e276, 1p |
| Abstrakt: |
The 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 assess MEC and improve therapies. A 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 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 was evaluated using ImageXpress from molecular devices. 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 were 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. The administration of HMD can effectively target MECs and their stem cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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