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Tamoxifen-induced [Ca2+]i rise and apoptosis in corneal epithelial cells.
Huang, Chorng-Chih; Cheng, He-Hsiung; Lin, Ko-Long; Cheng, Jin-Shiung; Tsai, Jeng-Yu; Liao, Wei-Chuan; Fang, Yi-Chien; Jan, Chung-Ren.
Afiliação
  • Huang CC; Department of Nursery, Tzu Hui Institute of Technology, Pingtung 926, Taiwan.
Toxicology ; 255(1-2): 58-64, 2009 Jan 08.
Article em En | MEDLINE | ID: mdl-18992300
ABSTRACT
The effect of tamoxifen on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability has not been explored in corneal epithelial cells. This study examined whether tamoxifen altered [Ca2+]i and viability in SIRC corneal epithelial cells. Tamoxifen at concentrations > or = 1 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 6 microM. The Ca2+ signal was reduced substantially by removing extracellular Ca2+. Tamoxifen induced Mn2+ quench of fura-2 fluorescence implicating Ca2+ influx. The Ca2+ influx was insensitive to Ca2+ entry inhibitors and protein kinase C modulators. After pretreatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), tamoxifen-induced [Ca2+]i rises were abolished; conversely, tamoxifen pretreatment abolished thapsigargin-induced [Ca2+]i rises. Inhibition of phospholipase C with U73122 did not change the [Ca2+]i rises. At concentrations of 5-30 microM, tamoxifen killed cells in a concentration-dependent manner. The cytotoxic effect of 15 microM tamoxifen was not reversed by prechelating cytosolic Ca2+ with BAPTA/AM. Apoptosis was induced by 5-30 microM tamoxifen. Tamoxifen (30 microM did not induce production of reactive oxygen species (ROS). Collectively, in SIRC cells, tamoxifen induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C-independent manner, and Ca2+ influx via unknown pathways. Tamoxifen-caused cytotoxicity was partly mediated by a Ca2+-independent apoptotic pathway.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tamoxifeno / Apoptose / Epitélio Corneano / Células Epiteliais / Antagonistas de Estrogênios Limite: Animals Idioma: En Revista: Toxicology Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tamoxifeno / Apoptose / Epitélio Corneano / Células Epiteliais / Antagonistas de Estrogênios Limite: Animals Idioma: En Revista: Toxicology Ano de publicação: 2009 Tipo de documento: Article