Exploitation of redox discrepancy in leukemia cells by a reactive oxygen species nanoscavenger for inducing cytotoxicity in imatinib resistant cells

Abstract

Chronic myeloid leukemia (CML) has been the hub of exhilarating progress in cancer therapy with the advent of imatinib mesylate. However, therapeutic selectivity and drug resistance are two major issues in imatinib based leukemia therapy prompting development of strategies to surmount imatinib resistance for effective CML therapy. Growing evidences advocate that, cancer cells exhibit augmented intrinsic reactive oxygen species (ROS), due to oncogenic stimulation, amplified metabolic activity, and mitochondrial dysfunction. Since ROS activates multidrug resistant proteins in CML cells, we hypothesized that an herbal molecule having ROS scavenging property may therefore enhance imatinib induced cell death in drug resistant cells by counteracting ROS mediated drug resistance. In the present study, we document to explore an approach to simultaneously deliver two drugs (imatinib, an anticancer drug for CML therapy and curcumin a ROS scavenger) using poly (lactide-co-glycolide) (PLGA) nanoparticles for drug resistant CML cells. Such a combinational approach will help to enhance the therapeutic efficacy of imatinib by utilizing ROS scavenging properties of curcumin in imatinib resistant cell line thereby sensitizing them to chemotherapy by activating alternative modalities of cell death.