ANTILEUKEMIC ACTIVITY OF PHENYLALANINE METHYL-ESTER (PME) - A LYSOSOMOTROPIC PEPTIDE METHYL-ESTER

Authors
Citation
Cs. Rosenfeld, ANTILEUKEMIC ACTIVITY OF PHENYLALANINE METHYL-ESTER (PME) - A LYSOSOMOTROPIC PEPTIDE METHYL-ESTER, Stem cells, 12(2), 1994, pp. 198-204
Citations number
12
Categorie Soggetti
Cytology & Histology","Biothechnology & Applied Migrobiology
Journal title
ISSN journal
10665099
Volume
12
Issue
2
Year of publication
1994
Pages
198 - 204
Database
ISI
SICI code
1066-5099(1994)12:2<198:AAOPM(>2.0.ZU;2-Z
Abstract
The antileukemic activities of the lysosomotropic compounds, such as p henylalanine methyl ester (PME), have received little attention. In th is study, a [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 tha n or equal to 75% blasts were used. Leukemic cells were treated with P ME 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 3 7-degrees-C, 50 mM PME caused greater than one log reduction of leukem ic cells in 13/16 acute myelogenous leukemia (AML), 7/9 acute lymphocy tic leukemia (ALL), and 8/8 in blast crisis of chronic myelogenous leu kemia (CML-BC) specimens. PME had less activity at 22-degrees-C than a t 37-degrees-C. PME was compared with 100 mug/ml 4-hydroperoxycyclopho sphamide (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 in dicate 1) PME has antileukemic activity and 2) 4HC has less antileukem ic activity than PME.