Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells.
Hum Exp Toxicol
; 28(1): 41-8, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19411560
ABSTRACT
The effect of fendiline on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) and proliferation has not been explored in human oral cancer cells. This study examined whether fendiline altered Ca(2+) levels and caused cell death in OC2 human oral cancer cells. [Ca(2+)](i) and cell viability were measured using the fluorescent dyes fura-2 and WST-1, respectively. Fendiline at concentrations above 10 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). The fendiline-induced Ca(2+) influx was sensitive to blockade of L-type Ca(2+) channel blockers. In Ca(2+)-free medium, after pretreatment with 50 microM fendiline, 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor)-induced [Ca(2+)](i) rises were inhibited; and conversely, thapsigargin pretreatment nearly abolished fendiline-induced [Ca(2+)](i) rises. Inhibition of phospholipase C with 2 microM U73122 did not change fendiline-induced [Ca(2+)](i) rises. At concentrations between 5 and 25 microM, fendiline killed cells in a concentration-dependent manner. The cytotoxic effect of 15 microM fendiline was not reversed by prechelating cytosolic Ca(2+) with BAPTA/AM. Collectively, in OC2 cells, fendiline induced [Ca(2+)](i) rises by causing Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx from L-type Ca(2+) channels. Furthermore, fendiline-caused cytotoxicity was not via a preceding [Ca(2+)](i) rise.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Boca
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Bloqueadores de los Canales de Calcio
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Fendilina
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Calcio
Límite:
Humans
Idioma:
En
Revista:
Hum Exp Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Taiwán