title: Pentamidine sensitizes chronic myelogenous leukemia K562 cells to TRAIL-induced apoptosis.
abstract: Pentamidine (PMD) is an anti-protozoa drug with potential anticancer activity. Here we show that PMD at clinically achievable plasma drug concentrations slightly inhibited the growth of human leukemia cell lines. PMD close to its therapeutic doses sensitized TRAIL-resistant K562 cells to the cytokine and potentiated TRAIL-induced apoptosis through activation of caspase-8 and -3. When we investigated the underlying mechanism, we observed that treatment with PMD increased DR5 expression at both mRNA and protein levels and down-regulated anti-apoptotic XIAP and Mcl-1 protein levels. This study provides a rationale for a more in-depth exploration into the combined treatment with PMD and TRAIL as a valuable strategy for leukemia therapy.
authors.affiliation: Department of Biochemistry, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Qiu
authors.forename: Jikai
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiao-shan
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D010419:Pentamidine / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; D010419:Pentamidine