Novel Approaches for Overcoming of Tumor Drug Resistance by Polyvalent Cationic Peptides

Background: Acquired resistance to various drugs is a key challenge for anticancer therapy.Earlier we have revealed a selective apoptosis of tumor cells induced by polyvalent cationic peptides (CPs) both in vitro and in vivo by inactivation their cell targets -multifunctional chaperone proteins nucleolin (NCL) and nucleophosmin (NPM).Here we applied Arg/ Lys-enriched CPs as well as CPs, conjugated with Doxorubicin (Dox) to induce cell death by nucleolar stress mechanisms both in Dox-sensitive breast cancer (BC) cells and in Dox-resistant ones.Molecular interactions between CP as ligand and cellular targets using computer modeling by docking have been done.Then, CP potential for anticancer therapy of various malignant tumors is discussed.Objective: An analysis of cell survival in breast cancer (BC) sublines that are sensitive or resistant to Doxorubicin (Dox) by cationic peptides (CPs) and conjugate CP +Dox. Results:The data indicate that Arg/Lys enriched CPs might be perspective agents for inducing BC cell apoptosis and for transport Dox or other drugs in tumor cells to overcome drug resistance. Conclusion:Molecular docking is effective tool for modeling and evaluating of interactions and competitive binding of CPs to their cellular targets.This approach is also useful for design novel peptides with high anticancer properties and low toxicity for patients.