Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer Cells

Author(s):

Tatiane Renata Fagundes*, Bruna Bortoleti, Priscila Camargo, Vírgínia Concato, Fernanda Tomiotto-Pellissier, Amanda Carloto, Carolina Panis, Marcelle Bispo, Fernando Macedo Junior, Ivete Conchon-Costa and Wander Rogério Pavanelli   Pages 1592 - 1600 ( 9 )

Abstract:

<p>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. <p> 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. <p> 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. <p> 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.</p>

Keywords:

Heterocyclics, thiohydantoins, breast cancer, ROS, MCF-7, apoptosis.

Affiliation:

Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR, Graduate Program in Biosciences and Biotechnology, Carlos Chagas Institute (ICC), Fiocruz, Curitiba, PR, Laboratory of Properties and Synthesis of Organic Substances, Department of Chemistry, Center of Exact Sciences, Londrina State University, PR, Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR, Graduate Program in Biosciences and Biotechnology, Carlos Chagas Institute (ICC), Fiocruz, Curitiba, PR, Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR, Laboratory of Tumor Biology, State University of Western Paraná, Francisco Beltrão, Paraná, Laboratory of Properties and Synthesis of Organic Substances, Department of Chemistry, Center of Exact Sciences, Londrina State University, PR, Graduate Program in Biosciences and Biotechnology, Carlos Chagas Institute (ICC), Fiocruz, Curitiba, PR, Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR, Laboratory of Immunoparasitology of Neglected Diseases and Cancer, State University of Londrina, PR

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