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Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF‐7 human breast carcinoma cell line
Author(s) -
Wang Shiyi,
Melkoumian Zaroui,
Woodfork Karen A.,
Cather Carrie,
Davidson Ann G.,
Wonderlin William F.,
Strobl Jeannine S.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199809)176:3<456::aid-jcp2>3.0.co;2-n
Subject(s) - mcf 7 , cell cycle progression , cancer research , cell culture , human breast , cell cycle , breast carcinoma , human cell , cell , carcinoma , biology , microbiology and biotechnology , oncology , medicine , breast cancer , cancer , biochemistry , genetics
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. J. Cell. Physiol. 176:456‐464, 1998. © 1998 Wiley‐Liss, Inc.