Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach

• Published in: Life (Basel, Switzerland) Vol. 12; no. 3; p. 383
• Main Authors: Haque, Absarul, Baig, Ghazanfar Ali, Alshawli, Abdulelah Saleh, Sait, Khalid Hussain Wali, Hafeez, Bilal Bin, Tripathi, Manish Kumar, Alghamdi, Badrah Saeed, Mohammed Ali, Hani S H, Rasool, Mahmood
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2022; MDPI
• Subjects: ABC transporter; Affinity; Amino acids; Antitumor agents; Binding; Binding sites; Cancer therapies; Carboplatin; Chemotherapy; Combinatorial analysis; Doxorubicin; Drugs; Gemcitabine; Homology; Hydrogen bonds; Ligands; Molecular docking; Multidrug resistance; multidrug resistance protein 1; Ovarian cancer; Paclitaxel; Phenotypes; Platinum; Proteins; Topotecan; Transmembrane domains; multidrug resistance; gemcitabine; multidrug resistance protein 1; ovarian cancer; carboplatin
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life12030383

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.