IADR Abstract Archives
High Throughput Screening Identifying New Inhibitory Compounds to Manage MEC
Objectives: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignant tumor, presenting a 5-year disease-free survival of 76%. The current treatment for MEC is surgical excision, while chemotherapy is often used for metastatic and unresectable tumors providing modest results. Recently, we have shown that epigenetic events play an important role in MEC behavior. We have also shown that drugs that target epigenetic modifications provide encouraging results. Based on the current lack of therapies crafted for MEC, we decided to explore the effects of a library of epigenetic drugs to identify potential new pharmacological agents capable of impacting the growth of MEC.
Methods: We used the UM-HMC3A MEC cell line to investigate the effects of epigenetic drugs in 2D and 3D culture models. We used high-precision liquid handlers to seed cells and administered drugs in a high-throughput format complemented by a high-throughput imaging system. Cell proliferation was accessed using propidium iodide to detect cell death, and tumor spheres were used to detect the effects of the library compounds on cancer stem cells (CSC). Data collected from cells was evaluated using ImageXpress from molecular devices.
Results: Administration of epigenetic drugs (library) impacted the proliferation of MEC cells. Eighty one compounds showed activity to induce cell death in MEC cells when compared to the control group, while 46 of these compounds pushed cell death rates above 50% of controls. Our preliminary data also found that 35 compounds had an inhibitory effect over CSC.
Conclusions: Our findings suggested that administration of epigenetic drugs can effectively target MEC cells and its stem cells. However, further studies are needed to elucidate the mechanism of action of these new inhibitors and their optimal concentration efficacy.
Methods: We used the UM-HMC3A MEC cell line to investigate the effects of epigenetic drugs in 2D and 3D culture models. We used high-precision liquid handlers to seed cells and administered drugs in a high-throughput format complemented by a high-throughput imaging system. Cell proliferation was accessed using propidium iodide to detect cell death, and tumor spheres were used to detect the effects of the library compounds on cancer stem cells (CSC). Data collected from cells was evaluated using ImageXpress from molecular devices.
Results: Administration of epigenetic drugs (library) impacted the proliferation of MEC cells. Eighty one compounds showed activity to induce cell death in MEC cells when compared to the control group, while 46 of these compounds pushed cell death rates above 50% of controls. Our preliminary data also found that 35 compounds had an inhibitory effect over CSC.
Conclusions: Our findings suggested that administration of epigenetic drugs can effectively target MEC cells and its stem cells. However, further studies are needed to elucidate the mechanism of action of these new inhibitors and their optimal concentration efficacy.