The role of catechin in electroporation of pancreatic cancer cells – Effects on pore formation and multidrug resistance proteins

Abstract

Catechin is a bioflavonoid known for its anti-cancer properties. In the present study, we combined theoretical and experimental approaches to reveal the potential of catechin application in the electroporation (EP) or electrochemotherapy (ECT) of pancreatic cancer cells. The molecular dynamics simulations were implemented to examine the interactions of catechin with a model of a membrane, its influence on the membrane’s thickness, and the impact of the catechin-membrane interaction on the pore formation. The data were confronted with experimental measurement of the threshold electric field required for permeabilization of pancreatic cancer cells to a fluorescent dye YO-PRO-1. Further, we examined the influence of catechin on cell viability following electroporation with cisplatin or calcium ions. Finally, we investigated the catechin impact on four proteins associated with multidrug resistance: P-glycoprotein, MRP1, BCRP, and LRP. We demonstrated that catechin may boost the effects of electroporation through various mechanisms: i) increasing the cell permeability prior to electroporation ii) increasing the electroporation threshold iii) sensitization of cells to chemotherapeutic compounds. We showed that catechin incubation influences mRNA levels and mitigates the immunoreactivity of Pgp, MRP1, BCRP, and LRP but these changes did not translate to the efficacy of electrochemotherapy.