title: Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine.
abstract: We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.
authors.affiliation: Departments of Special Medical Education Programs, Molecular and Cellular Oncology and Genitourinary Medical Oncology, Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Jendiroba
authors.forename: Jim
authors.initials: J
authors.lastname: Klostergaard
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Keyhani
authors.forename: Lance
authors.initials: L
authors.lastname: Pagliaro
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Freireich
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001752:Blast Crisis / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000473:pathology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000473:pathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C061800:N,N-dimethylsphingosine; D013110:Sphingosine