| Autor: |
Alsharabasy AM; CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway H91 W2TY, Ireland., Lagarias PI; Department of ChemoInformatics, Novamechanics Ltd., Nicosia 1070, Cyprus., Papavasileiou KD; Department of ChemoInformatics, Novamechanics Ltd., Nicosia 1070, Cyprus.; Department of Chemoinformatics, Novamechanics MIKE, Piraeus 18545, Greece.; Division of Data Driven Innovation, Entelos Institute, Larnaca 6059, Cyprus., Afantitis A; Department of ChemoInformatics, Novamechanics Ltd., Nicosia 1070, Cyprus.; Department of Chemoinformatics, Novamechanics MIKE, Piraeus 18545, Greece.; Division of Data Driven Innovation, Entelos Institute, Larnaca 6059, Cyprus., Farràs P; CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway H91 W2TY, Ireland.; School of Biological and Chemical Sciences, Ryan Institute, University of Galway, Galway H91 TK33, Ireland., Glynn S; CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway H91 W2TY, Ireland.; Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, University of Galway, Galway H91 YR71, Ireland., Pandit A; CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway H91 W2TY, Ireland. |
| Abstrakt: |
Hemin triggers intracellular reactive oxygen species (ROS) accumulation and enhances heme oxygenase-1 (HOX-1) activity, indicating its potential as an anticancer agent, though precise control of its intracellular levels is crucial. The study explores the impact of hemin and its derivatives, hemin-tyrosine, and hemin-styrene (H-Styr) conjugates on migration, HOX-1 expression, specific apoptosis markers, mitochondrial functions, and ROS generation in breast cancer cells. Molecular docking and dynamics simulations were used to understand the interactions among HOX-1, heme, and the compounds. Hemin outperforms its derivatives in inducing HOX-1 expression, exhibiting pro-oxidative effects and reducing cell migration. Molecular simulations show that heme binds favorably to HOX-1, followed by the other compounds, primarily through van der Waals and electrostatic forces. However, only van der Waals forces determine the H-Styr complexation. These interactions, influenced by metalloporphyrin characteristics, provide insights into HOX-1 regulation and ROS generation, potentially guiding the development of breast cancer therapies targeting oxidative stress. |
