title: Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines.
abstract: Overcoming MDR (multidrug resistance) phenomena is a crucial aspect of cancer chemotherapy research. Artemisinin and its derivatives have been found to inhibit the proliferation of cancer cells in the microM range. They poorly inhibited the function of P-glycoprotein and did not inhibit the function of MRP1-protein. The concentrations required to inhibit by 50% the function of P-glycoprotein are 110+/-5 microM. Artemisinin, artesunate and dihydroartemisinin efficiently decreased the mitochondrial membrane potential, leading to a decrease in intracellular ATP in all cell lines tested: by 30 to 50% at 5 microM. Artemisinin, artesunate and dihydroartemisinin increased cytotoxicity of pirarubicin and doxorubicin in P-glycoprotein-overexpressing K562/adr, and in MRP1-overexpressing GLC4/adr, with the delta(0.5) ranging from 200 to 860 nM, but not in their corresponding drug-sensitive cell lines. In this range of concentrations these compounds did not decrease the function of P-glycoprotein, suggesting a mechanism by which the drugs did not reverse MDR phenomenon at the P-glycoprotein level but at the mitochondrial level.
authors.affiliation: Laboratory of Physical Chemistry, Molecular and Cellular Biology, Faculty of Science, Burapha University, Bangsaen, Chonburi, Thailand.
authors.forename: Paiboon
authors.initials: P
authors.lastname: Reungpatthanaphong
authors.forename: Samlee
authors.initials: S
authors.lastname: Mankhetkorn
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002460:Cell Line; D018432:Drug Resistance, Multiple / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D037621:Artemisinins; D000077332:Artesunate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012717:Sesquiterpenes; C039060:artenimol; C031327:artemisinin; C421109:multidrug resistance-associated protein 1