TY - JOUR T1 - Development of a Dihydroartemisinin-resistant Molt-4 Leukemia Cell Line JF - Anticancer Research JO - Anticancer Res SP - 2807 LP - 2810 VL - 34 IS - 6 AU - JUNGSOO PARK AU - HENRY C. LAI AU - MALLIKA SINGH AU - TOMIKAZU SASAKI AU - NARENDRA P. SINGH Y1 - 2014/06/01 UR - http://ar.iiarjournals.org/content/34/6/2807.abstract N2 - Artemisinin generates cytotoxic free radicals when it reacts with iron. Its toxicity is more selective toward cancer cells because cancer cells contain a higher level of intracellular-free iron. We previously reported that dihydroartemisinin (DHA), an active metabolite of artemisinin, has selective cytotoxicity toward Molt-4 human lymphoblastoid cells. A concern is whether cancer cells could develop resistance to DHA after repeated administration, thus limiting its therapeutic efficacy. In the present study, we developed a DHA-resistant Molt-4 cell line (RTN) by exposing Molt-4 cells to gradually increasing concentrations of DHA in vitro. The half-maximal inhibitory concentration (IC50) of DHA for RTN cells is 7.1-times higher than that of Molt-4 cells. RTN cells have a higher growth rate than Molt-4 cells. In addition, we investigated the toxicities of two more potent synthetic artemisinin compounds, artemisinin dimer-alcohol and artemisinin-tagged holotransferrin toward RTN cells; RTN cells showed no significant cross-resistance to these compounds. ER -