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Original Article
The study of drug resistance properties of ABCG2 (ATP-binding cassette G2) in contact with thymoquinone, gallic acid, and hesperetin antioxidants
Javad Saffari_Chaleshtori
1, 2 
, Sayed Mohammad Shafiee
1, Keihan Ghatreh-Samani
3* , Narges Jalilian
41 Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
3 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
4 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
Abstract
Introduction: ATP-binding cassette (ABC) transporters are a group of intra membrane proteins that play key roles in the transmission and exchange of vital compounds on both sides of the membrane. These proteins can specially transport anti-cancer drugs out of cancer cells. ABCG2 is a member of this family that is extremely expressed in many cancers. This study, aims to evaluate the binding affinity of three antioxidants thymoquinone (TQ), gallic acid (GA), and hesperetin (HP) to ABCG2 compared with an anti-cancer drug, mitoxantrone (Mit), to export cells.
Methods: The PDB file of ABCG2 was obtained from the protein data bank server (http://www.rcsb.org) with ID: 5NJ3. After 200 stages of molecular docking running on ABCG2 protein in AutoDock v.4.2 software, the amino acids involved in the binding site of each compound were identified using the LigPlot+ software.
Results: HP had the lowest (-6.36 kcal/mol) and GA had the highest (-3.93 kcal/mol) binding energy in comparison with Mit (-0.06 kcal/mol) for binding to ABCG2. Effective concentration required to perform the reaction between ABCG2 was higher in GA (1.31 mM) than TQ (42.69 μM) and HP (21.74 μM). GA, HP, and TQ formed 17, 18, and 22 hydrogen and hydrophobic bonds at the binding site of ABCG2.
Conclusion: It seems that GA has the lowest affinity to make contact with ABCG2 binding site. So, GA tends to remain in the cell but TQ and HP tend to leave the cell easily via ABCG2 transporter.
Introduction: ATP-binding cassette (ABC) transporters are a group of intra membrane proteins that play key roles in the transmission and exchange of vital compounds on both sides of the membrane. These proteins can specially transport anti-cancer drugs out of cancer cells. ABCG2 is a member of this family that is extremely expressed in many cancers. This study, aims to evaluate the binding affinity of three antioxidants thymoquinone (TQ), gallic acid (GA), and hesperetin (HP) to ABCG2 compared with an anti-cancer drug, mitoxantrone (Mit), to export cells.
Methods: The PDB file of ABCG2 was obtained from the protein data bank server (http://www.rcsb.org) with ID: 5NJ3. After 200 stages of molecular docking running on ABCG2 protein in AutoDock v.4.2 software, the amino acids involved in the binding site of each compound were identified using the LigPlot+ software.
Results: HP had the lowest (-6.36 kcal/mol) and GA had the highest (-3.93 kcal/mol) binding energy in comparison with Mit (-0.06 kcal/mol) for binding to ABCG2. Effective concentration required to perform the reaction between ABCG2 was higher in GA (1.31 mM) than TQ (42.69 μM) and HP (21.74 μM). GA, HP, and TQ formed 17, 18, and 22 hydrogen and hydrophobic bonds at the binding site of ABCG2.
Conclusion: It seems that GA has the lowest affinity to make contact with ABCG2 binding site. So, GA tends to remain in the cell but TQ and HP tend to leave the cell easily via ABCG2 transporter.