Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach
Absarul Haque,
Ghazanfar Ali Baig,
Abdulelah Saleh Alshawli,
Khalid Hussain Wali Sait,
Bilal Bin Hafeez,
Manish Kumar Tripathi,
Badrah Saeed Alghamdi,
Hani S. H. Mohammed Ali,
Mahmood Rasool
Affiliations
Absarul Haque
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Ghazanfar Ali Baig
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abdulelah Saleh Alshawli
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Khalid Hussain Wali Sait
Gynecology Oncology Unit, Obstetrics and Gynecology Department, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia
Bilal Bin Hafeez
Department of Immunology and Microbiology, South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
Manish Kumar Tripathi
Department of Immunology and Microbiology, South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
Badrah Saeed Alghamdi
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Hani S. H. Mohammed Ali
Department of Biological Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mahmood Rasool
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.
