Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF-7 human breast carcinoma cell line

J Cell Physiol. 1998 Sep;176(3):456-64. doi: 10.1002/(SICI)1097-4652(199809)176:3<456::AID-JCP2>3.0.CO;2-N.


The mechanism of the G0/G1 arrest and inhibition of proliferation by quinidine, a potassium channel blocker, was investigated in a tissue culture cell line, MCF-7, derived from a human breast carcinoma. The earliest measurable effect of quinidine on the cell cycle was a decrease in the fraction of cells in S phase at 12 hr, followed by the accumulation of cells in G1/G0 phases at 30 hr. Arrest and release of the cell cycle established quinidine as a cell synchronization agent, with a site of arrest in early G1 preceding the lovastatin G1 arrest site by 5-6 hr. There was a close correspondence among the concentration-dependent arrest by quinidine in G1, depolarization of the membrane potential, and the inhibition of ATP-sensitive potassium currents, supporting a model in which hyperpolarization of the membrane potential and progression through G1 are functionally linked. Furthermore, the G1 arrest by quinidine was overcome by valinomycin, a potassium ionophore that hyperpolarized the membrane potential in the presence of quinidine. With sustained exposure of MCF-7 cells to quinidine, expression of the Ki67 antigen, a marker for cells in cycle, decreased, and apoptotic and necrotic cell death ensued. We conclude that MCF-7 cells that fail to progress through the quinidine-arrest site in G1 die.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Arrhythmia Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • G1 Phase / drug effects
  • G1 Phase / physiology*
  • Humans
  • Ionophores / pharmacology
  • Ki-67 Antigen / biosynthesis
  • Lovastatin / pharmacology
  • Membrane Potentials / drug effects
  • Potassium Channels / physiology*
  • Quinidine / pharmacology
  • Resting Phase, Cell Cycle / drug effects
  • Resting Phase, Cell Cycle / physiology
  • S Phase / drug effects
  • S Phase / physiology
  • Time Factors
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / metabolism
  • Valinomycin / pharmacology


  • Anti-Arrhythmia Agents
  • Antineoplastic Agents
  • Ionophores
  • Ki-67 Antigen
  • Potassium Channels
  • Valinomycin
  • Lovastatin
  • Quinidine