TY  - CONF
AU  - Ostojić, Marija
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Dobričić, Vladimir
AU  - Grahovac, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5477
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of death worldwide and the fourth
in Europe with a 5-year survival rate. The common cause of treatment failure in PDAC patients is
multidrug resistance (MDR) due to the increased expression of plasma membrane efflux pumps that
limit the intracellular uptake and retention of numerous xeno- and endobiotics. As the 93.3% of
pancreatic carcinomas expressed P-glycoprotein (P-gp-MDR1/ABCB1) and 31% co-expressed multidrug
resistance protein 1 (MRP1/ABCC1) with MDR1 P-gp, the inhibition of these pumps may be the target
for novel anticancer drugs.
We used the FRED 3.2.0.2 software to predict the affinity of I1-imidazoline receptor ligand rilmenidine
within the binding site of P-gp-MDR1/ABCB1 and MRP1/ABCC1, and flow cytometry to evaluate the
effect of rilmenidine phosphate and rilmenidine fumarate on the efflux pumps in PDAC cells in vitro.
The results of the molecular docking studies indicate that rilmenidine has the binding affinity for both
P-gp-MDR1/ABCB1 and MRP1/ABCC1 efflux pumps. While, in vitro studies show that rilmenidine
fumarate has better potential to inhibit Calcein AM efflux than rilmenidine phosphate, and it did so in a
dose-dependent manner.
Our results indicate that rilmenidine has the affinity to bind to MDR efflux pumps and to inhibit their
activity. This potential of rilmenidine to overcome multidrug resistance in PDAC should be further
investigated in order to develop more effective PDAC therapy.
PB  - COST Action 17104 (STRATAGEM)
C3  - STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 5th Annual Meeting, 29th June - 1st July 2022, Coimbra, Portugal
T1  - Rilmenidine binds to and inhibits the activity of MDR pumps in pancreatic ductal adenocarcinoma
SP  - 80
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5477
ER  - 

@conference{
author = "Ostojić, Marija and Đurić, Ana and Srdić-Rajić, Tatjana and Dobričić, Vladimir and Grahovac, Jelena",
year = "2022",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of death worldwide and the fourth
in Europe with a 5-year survival rate. The common cause of treatment failure in PDAC patients is
multidrug resistance (MDR) due to the increased expression of plasma membrane efflux pumps that
limit the intracellular uptake and retention of numerous xeno- and endobiotics. As the 93.3% of
pancreatic carcinomas expressed P-glycoprotein (P-gp-MDR1/ABCB1) and 31% co-expressed multidrug
resistance protein 1 (MRP1/ABCC1) with MDR1 P-gp, the inhibition of these pumps may be the target
for novel anticancer drugs.
We used the FRED 3.2.0.2 software to predict the affinity of I1-imidazoline receptor ligand rilmenidine
within the binding site of P-gp-MDR1/ABCB1 and MRP1/ABCC1, and flow cytometry to evaluate the
effect of rilmenidine phosphate and rilmenidine fumarate on the efflux pumps in PDAC cells in vitro.
The results of the molecular docking studies indicate that rilmenidine has the binding affinity for both
P-gp-MDR1/ABCB1 and MRP1/ABCC1 efflux pumps. While, in vitro studies show that rilmenidine
fumarate has better potential to inhibit Calcein AM efflux than rilmenidine phosphate, and it did so in a
dose-dependent manner.
Our results indicate that rilmenidine has the affinity to bind to MDR efflux pumps and to inhibit their
activity. This potential of rilmenidine to overcome multidrug resistance in PDAC should be further
investigated in order to develop more effective PDAC therapy.",
publisher = "COST Action 17104 (STRATAGEM)",
journal = "STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 5th Annual Meeting, 29th June - 1st July 2022, Coimbra, Portugal",
title = "Rilmenidine binds to and inhibits the activity of MDR pumps in pancreatic ductal adenocarcinoma",
pages = "80-80",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5477"
}

Ostojić, M., Đurić, A., Srdić-Rajić, T., Dobričić, V.,& Grahovac, J.. (2022). Rilmenidine binds to and inhibits the activity of MDR pumps in pancreatic ductal adenocarcinoma. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 5th Annual Meeting, 29th June - 1st July 2022, Coimbra, Portugal
COST Action 17104 (STRATAGEM)., 80-80.
https://hdl.handle.net/21.15107/rcub_farfar_5477

Ostojić M, Đurić A, Srdić-Rajić T, Dobričić V, Grahovac J. Rilmenidine binds to and inhibits the activity of MDR pumps in pancreatic ductal adenocarcinoma. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 5th Annual Meeting, 29th June - 1st July 2022, Coimbra, Portugal. 2022;:80-80.
https://hdl.handle.net/21.15107/rcub_farfar_5477 .

Ostojić, Marija, Đurić, Ana, Srdić-Rajić, Tatjana, Dobričić, Vladimir, Grahovac, Jelena, "Rilmenidine binds to and inhibits the activity of MDR pumps in pancreatic ductal adenocarcinoma" in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 5th Annual Meeting, 29th June - 1st July 2022, Coimbra, Portugal (2022):80-80,
https://hdl.handle.net/21.15107/rcub_farfar_5477 .