Quercetin, Menadione, Doxorubicin combination as a potential alternative to Doxorubicin monotherapy of acute lymphoblastic leukemia

Abstract Doxorubicin is a widely used chemotherapeutic drug, effective on patients with acute lymphoblastic leukemia but associated with significant long term cardio-toxicity. Menadione (vitamine K3) and the flavonoid quercetin are known as strong apoptogens in human leukemia Jurkat T cells. We explored the potential synergic cytotoxic effects of doxorubicin in association with quercetin and Menadione in this cellular model for acute lymphoblastic leukemia. Cellular viability, apoptosis, necrosis oxidative stress and cellular cycle were determined by flow cytometry utilizing Jurkat lymphoblasts labeled with Annexin V-FITC/7-AAD, CM-H2DCFDA/7-AAD and propidium iodide respectively. Results indicate a dose-dependent oxidative-stress generation, cell cycle arrest and apoptosis induction by doxorubicin alone, correlated with a decrease of the required doses when the anticancer drug was associated with quercetin and menadione, hence supporting the theory of an additive cytotoxic effect on leukemia cells. Introducing QC-MD combinations in leukemia doxorubicin-based treatment could significantly increase the treatment’s efficacy. The main mechanism responsible for this effect appears to be the increase in DOX affinity for DNA, which enables lowering of the therapeutic dose.