In vitro and in vivo antitumor activity of the interferon inducer bropirimine.
In vivo and in vitro antitumor effects of an interferon (IFN)-alpha inducer, bropirimine (2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone), were examined in the murine tumor system. The antitumor effects were studied in Meth A cells, which were the most sensitive to bropirimine in the murine cell lines tested. The direct inhibitory activity of the drug was not reduced when Meth A cells were incubated with bropirimine and anti-IFNs, indicating that the inhibition is not due to autocrine IFN induction from tumor cells. The drug partially inhibited the uptake of [3H]thymidine, [3H]uridine and [3H]leucine. Cell cycle analysis with flow cytometry showed that the drug decreased G0/G1 phase and increased G2/M phase Meth A cells. The drug administered i.p. exhibited a remarkable antitumor effect against Meth A cells which were implanted i.p. These results suggested that the drug induced the in vivo antitumor effect by its direct antitumor activity.
Shimizu
M
M
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Oh-Hashi
F
F
Tsukagoshi
S
S
Iwaguchi
T
T
Kataoka
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005354:Fibrosarcoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007369:Interferon Inducers; D003596:Cytosine; C033560:bropirimine