Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints
Sweet, S.; Singh, G.
Cancer Research 55(22): 5164-5167
1995
ISSN/ISBN: 0008-5472 PMID: 7585566 Document Number: 451568
Agents that disrupt mitochondrial function were used to monitor the contribution of ATP to cell cycle progression. Following nontoxic exposure to these agents, now cytometric analysis of the cell population showed a significant increase in the proportion of cells in G-1 at low doses of the agent and in G-2-M at higher doses, in accordance with the degree of ATP reduction induced by the compound. These data indicate that cycling cells must maintain a minimal ATP content to satisfy the energy requirement of the checkpoint that allows passage through G-1 into S phase. Once committed, successful passage through G-2 into mitosis is also conditional upon maintenance of a critical ATP content sufficient to satisfy the second energy-sensitive checkpoint that exists at this transition. These data establish a foundation for future investigations into the energy dependence of cell cycle events and propose novel means for cell cycle intervention.