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Cytotoxicity studies of 2‐hydroxymethyl‐1‐naphthol diacetate on K + currents in neoplastic plasma cells
Author(s) -
Shen Ai Yu,
Li Hui Fang,
Lu Shih I.
Publication year - 1999
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199905)47:1<1::aid-ddr1>3.0.co;2-#
Subject(s) - chemistry , quinidine , tetraethylammonium , depolarization , biophysics , intracellular , medicine , potassium , biochemistry , biology , organic chemistry
The present study investigated the effects of 2‐hydroxymethyl‐1‐naphthol diacetate (TAC) on cell proliferation and K + currents in RPMI‐8226 human myeloma cells. In cells with intracellular Ca 2+ concentration ([Ca 2+ ] i ) = 10 nM, depolarizing square pulses from a holding potential of –80 mV elicited instantaneous outward current with slow inactivation, corresponding to voltage‐activated K + current. TAC (1–100 μM) inhibited I K(V) in a concentration‐dependent manner. A23187 (1 μM), a Ca 2+ ionophore, can potentiate Ca 2+ ‐activated K + current (I K(Ca) ). Tetraethylammonium chloride (10 mM) caused a small decrease in the amplitude of I K(Ca) elicited by A23187, whereas TAC (30 μM) and quinidine (10 μM) decreased I K(Ca) more effectively. The present results show that TAC directly blocks voltage‐ and Ca 2+ ‐activated K + currents in human myeloma cells. TAC inhibited both cell proliferation and voltage‐activated K + current with an effective dose inducing half‐maximum effects at 3.8 ± 0.8 μM and 10 ± 1.5 μM, respectively. The present study suggests that the cytotoxic effect of TAC in cancer cells may be partially explained by blockade of K + channels. The delocalization energy of TAC and other analogs was employed to compare their ability to block the voltage‐activated K + channel in myeloma cells. It was found that naphthol derivatives‐mediated blockade of voltage‐activated K + channel might relate to the level of delocalization energy and molecular volume. Drug Dev. Res. 47:1–8, 1999. © 1999 Wiley‐Liss, Inc.