Potentiation of growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine by 2'-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas.
Growth-inhibitory activity of 2'-deoxycoformycin (DCF) and 9-beta-D-arabinofuranosyladenine (Ara-A) used either singly or in combination was assessed in 30 human cultured cell lines (seven T-cell, nine B-cell, five non-T,non-B and nine myeloid cell lines) derived from leukemias and lymphomas. DCF had little activity even at 100 microM on any of the cell lines, while Ara-A had an obvious inhibitory effect on them, especially on non-T,non-B cell lines at 10 microM or less. Lymphoid cell lines were apparently more sensitive to the combined use of Ara-A and DCF than myeloid cell lines. DCF potentiated the antiproliferative activity of Ara-A not only in T-cell lines with high adenosine deaminase (ADA) activity, but also in some other cell lines with low ADA activity. DCF was stable in the culture medium, but Ara-A in the medium containing cultured cells was rapidly inactivated. DCF completely inhibited the inactivation of Ara-A in the medium containing P12/ICH or NALM-6, but not in the medium containing Daudi. This suggests that there is some unknown mechanism(s) of inactivation of Ara-A other than ADA in Daudi, which was insensitive to Ara-A in the presence of 1 microM DCF. The capacity of DCF to inhibit degradation of Ara-A in the medium containing these cultured cells correlated with the level of Ara-A sensitivity potentiated by DCF. In all seven T-cell lines, seven of the nine B-cell lines, all five non-T,non-B cell lines, and only three of nine myeloid cell lines, the IC50 value for Ara-A decreased to 5 microM or less in the presence of 1 microM DCF. These results suggest that the combination of DCF and Ara-A may be effective against various types of lymphoid malignancies and some myeloid leukemias.
Kuroki
Y
Y
Hematology-Oncology and Clinical Cancer Chemotherapy Division, National Cancer Center, Tokyo.
Shimoyama
M
M
Inaba
S
S
Hirose
M
M
D000243:Adenosine Deaminase / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004355:Drug Stability; D004357:Drug Synergism; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008223:Lymphoma / Q000473:pathology; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014740:Vidarabine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D000243:Adenosine Deaminase; D014740:Vidarabine