Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer Cells
Tatiane Renata Fagundes1, Bruna Bortoleti2, Priscila Camargo3
1Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR, Brazil.
Background:
Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being highly effective with significant adverse effects. Thiohydantoins are biologically active heterocyclic compounds reported for several biological activities, including anticarcinogenic properties, etc. This work aims to assess the use of thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells.
Methods:
MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7 cells. Cell volume measurement and analysis were performed by flow cytometry. Fluorescence analysis was carried out to determine patterns of cell death induced by thiohydantoins.
Results:
The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast tumor cells. An increase in the ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial depolarization, and increased fluorescence for annexin-V and caspase-3 were also observed. These findings indicate cell death by apoptosis and increased autophagic vacuoles, stopping the cell cycle in the G1/ G0 phase.
Conclusion:
Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the increase in ROS production. This phenomenon changes tumorigenic pathways, which halt the cell cycle in G1/G0. This is an essential checkpoint for DNA errors, which may have altered how cells produce energy, causing a decrease in mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy, a vital process linked to a decrease in lysosomal viability and thus considered a cell death and tumor suppression mechanism.
