Evaluation of quercetin cytoxicity on human colon tumor cell line and its possibile role as chemoresistance modulator

Abstract The development of the resistance to antineoplastic drugs is a major issue in the cancer treatment. Multidrug Resistance (MDR) of cancer cells is often associated with over-expression of P-glycoprotein (P-gp), a plasma membrane transporter. Recently, flavonoids, minor constituents of diet responsible for several biological activities, such as strong antioxidant and antiproliferative properties have been evaluated as MDR modulators with controversial results. Several studies have displayed that polyphenols in certain conditions can act as pro-oxidants, showing cytotoxic and mutagenic effects. We have evaluated the effects of quercetin on tumor cell proliferation and its potential effectiveness as MDR reverser influencing the cytoxicity of antineoplastic drugs (doxorubicin). LoVo wild-type, a human colon adenocarcinoma cell line and LoVo Dx, a multidrug resistant variant cell line, in the presence of quercetin showed a concentration and time-dependent susceptibility to flavonoid toxicity. The cell line WT showed a decrease in viability after 24 hours of quercetin treatment (IC50 = 70M), while the cell line Dx, were less affected (IC50 = 200 M). With respect to the MDR modulating activity, quercetin was found not to be a P-gp inhibitor compared to the well established P-gp reversers, Verapamil and Cyclosprin A. Conversely, quercetin protected both cell lines against doxorubicin toxicity.