Stem Cells, Vol 12, 198-204, Copyright © 1994 by AlphaMed Press
Antileukemic activity of phenylalanine methyl ester (PME): a lysosomotropic peptide methyl ester
CS Rosenfeld
Western Pennsylvania Cancer Institute, Pittsburgh.
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.
