title: Antileukemic activity of phenylalanine methyl ester (PME): a lysosomotropic peptide methyl ester.
abstract: The antileukemic activities of the lysosomotropic compounds, such as phenylalanine methyl ester (PME), have received little attention. In this study, a 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate the antileukemic activity of PME. Leukemic specimens from untreated patients that contained greater than or equal to 75% blasts were used. Leukemic cells were treated with PME at 37 degrees C and 22 degrees C in concentrations ranging from 0.5 to 50 mM. Normal blood mononuclear cells served as controls. At both 37 degrees C and 22 degrees C, the recovery of normal peripheral blood cells was approximately 28% following incubation with 50 mM PME. At 37 degrees C, 50 mM PME caused greater than one log reduction of leukemic cells in 13/16 acute myelogenous leukemia (AML), 7/9 acute lymphocytic leukemia (ALL), and 8/8 in blast crisis of chronic myelogenous leukemia (CML-BC) specimens. PME had less activity at 22 degrees C than at 37 degrees C. PME was compared with 100 micrograms/ml 4-hydroperoxycyclophosphamide (4HC). In contrast to PME, 4HC was associated with a greater than one log reduction of leukemic cells in only 1/13 AML, 1/3 ALL and 0/6 CML-BC specimens. 4HC activity exceeded PME activity in only one case each of ALL and prolymphocytic leukemia (PLL). In a case of CD34+ B cell ALL, synergy of PME and 4HC was demonstrated. These studies indicate 1) PME has antileukemic activity and 2) 4HC has less antileukemic activity than PME.
authors.affiliation: Western Pennsylvania Cancer Institute, Pittsburgh.
authors.forename: C S
authors.initials: CS
authors.lastname: Rosenfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001752:Blast Crisis / Q000188:drug therapy; D002648:Child; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C034515:phenylalanine methyl ester; D010649:Phenylalanine; D003520:Cyclophosphamide; C011272:perfosfamide