Inhibitory effect of a nucleoside analog, acyclovir, on leukemia cells.
Acyclovir (ACV), a nucleoside analog, has been demonstrated previously to suppress selectively the proliferation of NIH3T3 fibroblastic cells transformed by either v-abl or bcr-abl gene transfection. From a viewpoint of clinical application of ACV, we investigated whether ACV inhibited the growth of leukemia cells expressing either p210 BCR-ABL or p185BCR-ABL. Acyclovir exerted an inhibitory effect on OM9;22 cells, p185BCR-ABL expressing cells, in a dose-dependent manner. Despite no down-modulation of a BCR-ABL tyrosine kinase activity or its expression was observed after treatment with ACV, cell cycle analysis demonstrated synchronization of OM9;22 cells at the G0/G1 phase. This suggests that, although ACV does not directly act on BCR-ABL tyrosine kinase, ACV may exert its inhibitory effect on some leukemia cell lines via alterations of the cell cycle. Although selective inhibition of Philadelphia chromosome-positive leukemia cell growth was not apparent, our data provides a therapeutic possibility for ACV in the treatment for leukemia.
Nishimaki
J
J
First Department of Internal Medicine, Tokyo Medical College, Japan.
Miyazawa
K
K
Gotoh
A
A
Yoshikawa
O
O
Ohyashiki
K
K
Toyama
K
K
D000212:Acyclovir / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005069:Evaluation Studies as Topic; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013937:Thymidine Kinase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D013937:Thymidine Kinase; D016044:Fusion Proteins, bcr-abl; D000212:Acyclovir