Growth inhibitory effect of N-(phosphonacetyl)-L-aspartic acid on human myeloid leukemia-derived cell lines and modulation by dipyridamole.
Dipyridamole (DIP) inhibited the uptake of tritiated thymidine (TdR), deoxyuridine (UdR) and uridine (UR) in myeloid leukemia-derived cell lines, PL-21 and KCL-22. DIP also inhibited the growth of PL-21 (50% inhibitory concentrations, IC50, 15 microM) and KCL-22 (IC50, 3.0 microM). PALA inhibited the growth of PL-21 (IC50, 68 microM) and KCL-22 (IC50, 62 microM). The growth inhibition by PALA was significantly enhanced by the addition of 1 microM (PL-21) and 0.1 microM (KCL-22) of DIP. The inhibitory effect of PALA or PALA with DIP was completely abolished by the addition of 50 microM of UR in both cell cultures. Clinical evaluation of PALA in combination with DIP is warranted for the treatment of myeloid leukemia.
Taguchi
H
H
Department of Internal Medicine, Kochi Medical School, Japan.
Kubonishi
I
I
Miyoshi
I
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007938:Leukemia; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D000970:Antineoplastic Agents; D001224:Aspartic Acid; D004176:Dipyridamole; C013195:sparfosic acid; D010746:Phosphonoacetic Acid