Involvement of Ca2+ influx in the mechanism of tamoxifen-induced apoptosis in HepG2 human hepatoblastoma cells

被引：52

作者：

Kim, JA

King, YS

Jung, MW

Lee, SH

Lee, YS ^{[1
]}

机构：

[1] Kwandong Univ, Coll Med, Dept Physiol, Kangnung 210701, South Korea

[2] Yeungnam Univ, Coll Pharm, Physiol Sect, Kyongsan 712749, South Korea

来源：

CANCER LETTERS | 1999年 / 147卷 / 1-2期

基金：

新加坡国家研究基金会;

关键词：

tamoxifen; apoptosis; HepG2; cell; intracellular calcium ion; non-selective cation channel;

D O I：

10.1016/S0304-3835(99)00284-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The signaling mechanism of tamoxifen (TAM)-induced apoptosis was investigated in HepG2 human hepatoblastoma cells which do not express the estrogen receptor (ER). TAM induced cytotoxicity and DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TAM increased the intracellular concentration of Ca2+. This effect was completely inhibited by the extracellular Ca2+ chelation with EGTA. TAM also induced a Mn2+ influx, indicating that TAM activated Ca2+ influx pathways. This action of TAM was significantly inhibited by flufenamic acid (FA), a known non-selective cation channel blocker. Quantitative analysis of apoptosis by flow cytometry revealed that treatment with either FA or BAPTA, an intracellular Ca2+ chelator, significantly inhibited TAM-induced apoptosis. These results suggest that intracellular Ca2+ signals may play a central role in the mechanism of the TAM-induced apoptotic cell death in ER-negative HepG2 cells. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：115 / 123

页数：9

共 41 条

[1] Characterization of the ''estrogenicity'' of tamoxifen and raloxifene in HepG2 cells: Regulation of gene expression from an ERE controlled reporter vector versus regulation of the endogenous SHBG and PS2 genes [J].