NDLI: Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line

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Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line

Content Provider	Springer Nature Link
Author	Hwang, Jung Jin Kim, Ha Na Kim, Jean Cho, Dong Hyung Kim, Mi Joung Kim, Yong Sook Kim, Yunha Park, Sung Jin Koh, Jae Young
Copyright Year	2010
Abstract	Treatment of MCF-7 cells with tamoxifen induced vacuole formation and cell death. Levels of the autophagy marker, microtubule-associated protein light chain 3 (LC3)-II also increased, and GFP-LC3 accumulated in and around vacuoles in MCF-7 cells exposed to tamoxifen, indicating that autophagy is involved in tamoxifen-induced changes. Live-cell confocal microscopy with FluoZin-3 staining and transmission electron microscopy with autometallographic staining revealed that labile zinc(II) ion (Zn2+) accumulated in most acidic LC3(+) autophagic vacuoles (AVs). Chelation of Zn2+ with N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) blocked the increase in phospho-Erk and LC3-II levels, and attenuated AV formation and cell death. Conversely, the addition of ZnCl2 markedly potentiated tamoxifen-induced extracellular signal-regulated kinase (Erk) activation, autophagy and cell death, indicating that Zn2+ has an important role in these events. Tamoxifen-induced death was accompanied by increased oxidative stress and lysosomal membrane permeabilization (LMP) represented as release of lysosomal cathepsins into cytosol. Treatment with the antioxidant N-acetyl-l-cysteine (NAC) blunted the increase in Zn2+ levels and reduced LC3-II conversion, cathepsin D release and cell death induced by tamoxifen. And cathepsin inhibitors attenuated cell death, indicating that LMP contributes to tamoxifen-induced cell death. Moreover, TPEN blocked tamoxifen-induced cathepsin D release and increase in oxidative stress. The present results indicate that Zn2+ contributes to tamoxifen-induced autophagic cell death via increase in oxidative stress and induction of LMP.
Starting Page	997
Ending Page	1013
Page Count	17
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	23
Issue Number	6
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-06-04
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cathepsin Extracellular signal-regulated kinase Lysosome Lysosomal membrane permeabilization Microtuble-associated protein light chain 3 Oxidative stress Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line