A new class of reversible cell cycle inhibitors.
The effects of three compounds on the cell cycle of HL-60 promyeloid leukemia cells has been examined. Ciclopirox olamine, an antifungal agent, and the compound Hoechst 768159 reversibly block the cell cycle at a point occurring roughly 1 h before the arrest mediated by aphidicolin, an inhibitor of DNA polymerase alpha activity, which acts in early S phase. Similar results are also obtained with the compound mimosine, a plant amino acid. Based on these data, it is concluded that all three agents inhibit cell cycle traverse at or very near the G1/S phase boundary and identify a previously undefined reversible cell cycle arrest point.
Hoffman
B D
BD
Harvard Medical School, Boston, Massachusetts.
Hanauske-Abel
H M
HM
Flint
A
A
Lalande
M
M
D000935:Antifungal Agents / Q000494:pharmacology*; D016590:Aphidicolin; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D000077768:Ciclopirox; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008898:Mimosine / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000935:Antifungal Agents; D004224:Diterpenes; D011728:Pyridones; D013844:Thiazoles; D000077768:Ciclopirox; D016590:Aphidicolin; D008898:Mimosine; C063742:HOE 768159; D004257:DNA Polymerase II