Mechanism of action of the synthetic imidazole compound YM 534 on human promyelocytic leukemia line HL-60 cells.
The effects of a novel anti-cancer drug, YM 534 on human promyelocytic leukemia line HL-60 cells were investigated. The growth of the cells was completely inhibited with an IC50 of 2.5 X 10(-6) M. The incorporation of 3H-thymidine or 3H-uridine into acid insoluble fraction of the cells was completely inhibited at a 10(-4) M concentration of the drug. However, that of 3H-leucine was suppressed by only 32% at this drug concentration. The single strand scission of DNA of the cells as revealed by alkali sucrose density gradient centrifugation was induced by YM 534 at a 10(-4)M concentration for 60 min. When PM2 DNA in a cell-free system was examined in the presence or absence of reducing agent, no damage to DNA was observed at a 10(-4)M YM 534. The processing of preribosomal to ribosomal RNA of HL-60 cells was retarded at a 10(-5) M level of the drug.
Kanamaru
R
R
Department of Clinical Cancer Chemotherapy, Tohoku University, Sendai, Japan.
Ishioka
C
C
Konishi
Y
Y
Ishikawa
A
A
Shibata
H
H
Wakui
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D012322:RNA Precursors / Q000187:drug effects / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D012335:RNA, Ribosomal / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007093:Imidazoles; D012322:RNA Precursors; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal