Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 28, Issue 2, Pages 199-208Publisher
KARGER
DOI: 10.1159/000331731
Keywords
4-aminopyridine; Acute myeloid leukemia; Apoptosis; Mitochondria; Purinergic receptors
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Funding
- National Natural Science Foundation of China [81001051]
- Harbin Research Funds for Science Innovation Young Scholar [2008RFQXS100]
- Heilongjiang Provincial Natural Science Foundation of China [QC2010019]
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4-AP, a voltage-gated potassium channel blocker, was identified to exert critical pro-apoptotic properties in various types of cancer cells. The present study aims to explore the effect of 4-AP on the apoptosis of human AML cells and the underlying mechanism. We found 4-AP inhibited the proliferation and induces apoptosis in both AML cell lines and primary cultured human AML cells. The apoptosis of AML cells after 4-AP treatment was further confirmed by the disruption of mitochondrial membrane potential (MMP) and activation of caspase 3 and 9. 4-AP inhibited Kv currents in NB4, HL-60 and THP-1 cells. Furthermore, 4-AP induced significant increment in [Ca2+](i), which were inhibited by KN-62, a specific blocker of P2X7 receptors. KN-62 also abrogated 4-AP induced apoptosis. Knockdown of P2X7 receptor by small interfering RNA blocked the effect of 4-AP. Conclusively, this study indicated that 4-AP promotes apoptosis in human AML cells via increasing [Ca2+](i) through P2X7 receptor. Copyright (C) 2011 S. Karger AG, Basel
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