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Zinc depletion‐induced apoptosis is mediated through Ca 2+ ‐ dependent depolarization of mitochondria membrane in human breast cancer MDA‐MB‐231 cells
Author(s) -
Lin Alice,
Xu Zhaoming
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb285
Subject(s) - depolarization , apoptosis , membrane potential , mitochondrion , chemistry , microbiology and biotechnology , inner mitochondrial membrane , zinc , biology , biophysics , biochemistry , organic chemistry
We have previously shown that zinc depletion induces a Ca 2+ ‐ dependent apoptosis in MDA‐MB‐231 cells. This zinc depletioninduced apoptosis is associated with an increased Bax:Bcl‐2 ratio and an elevated caspase‐9 and −3 activities while caspase‐8 activity remains unchanged. We hypothesized that Ca 2+ ‐dependent depolarization of the mitochondrial membrane is involved in zinc depletion‐induced apoptosis. To test this hypothesis, MDA‐MB‐ 231 cells were cultured in DMEM+10% FBS for 3 days followed by treating the cells with N,N,N′,N′‐tetrakis[2‐ pyridylmethyl]ethylenediamine (TPEN; 20μM) alone for 0–24h or in the presence of 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester (BAPTA; 0–20μM) for 24h. Mitochondrial membrane potential was assessed by a DiOC 6 flow cytometric assay. TPEN caused depolarization of the mitochondrial membrane in a treatment duration‐dependent manner (2–24h; R 2 =0.99). BAPTA reduced TPEN‐induced depolarization of the mitochondrial membrane by 62–79%. Collectively, these results indicated that zinc depletion‐induced apoptosis was mediated through a Ca 2+ ‐dependent depolarization of the mitochondrial membrane in MDA‐MB‐231 cells. Supported by NSERC.