RT Journal Article
SR Electronic
T1 Development of a Dihydroartemisinin-resistant Molt-4 Leukemia Cell Line
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2807
OP 2810
VO 34
IS 6
A1 JUNGSOO PARK
A1 HENRY C. LAI
A1 MALLIKA SINGH
A1 TOMIKAZU SASAKI
A1 NARENDRA P. SINGH
YR 2014
UL http://ar.iiarjournals.org/content/34/6/2807.abstract
AB 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.