[Mechanism of arsenic trioxide induced apoptosis in cultured human lens epithelium cells].
OBJECTIVE
To study cytotoxic effects of arsenic trioxide (As2O3) on the human lens epithelium cells and to identify the biological mechanism for these effects.


METHODS
In this experimental study, human lens epithelium cells (FHL124 cells) were cultured in Eagle's minimum essential medium supplemented with 5% fetal calf serum. The effects of As2O3 on FHL124 cells growth were tested by MTT, and apoptosis was detected by TUNEL assay. Gene changes were detected by real-time PCR (Taqman). As2O3-induced changes in cell calcium level were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation.


RESULTS
As2O3 inhibited the growth of FHL 124 cells in vitro in a dose-dependent manner, given an IC50 value of 1.5 micromol/L. As2O3 induced apoptosis of FHL124 cells as showed by TUNEL assay. As2O3 provoked an endoplasmic reticulum (ER) stress response identified through an up regulation of EIF2A, ERN1 and ATF6 (F = 8.51, P = 0.0005). As2O3 depleted the calcium store and consequently lead to a decrease of calcium signaling (P = 0.0018). Moreover, As2O3 had a moderate effect on the calcium influx pathway.


CONCLUSIONS
As2O3 inhibits the growth and induces apoptosis of human lens epithelium cells. As2O3 provokes an ER stress which could be the cause of apoptic processes.
Zhang
Hong
H
Eye Hospital, the First Clinical Hospital of Harbin Medical University, Harbin 150001, China. dr.hzhang2007@hotmail.com
Liu
Ping
P
Yu
Xu-hui
XH
Song
Zhen
Z
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide