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Zinc induced apoptosis in HEP‐2 cancer cells: The role of oxidative stress and mitochondria
Author(s) -
Rudolf Emil,
Rudolf Kamil,
Cervinka Miroslav
Publication year - 2005
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520230206
Subject(s) - mitochondrion , apoptosis , cytochrome c , reactive oxygen species , microbiology and biotechnology , oxidative stress , chemistry , cytoplasm , caspase , apoptosis inducing factor , programmed cell death , cancer cell , biochemistry , biology , cancer , genetics
Induction of apoptosis by zinc sulfate was investigated during 96 h exposure on the cancer Hep‐2 cell line. During 48 h of exposure, zinc translocated into mitochondria and stimulated production of reactive oxygen species (ROS), affected cellular GSH management and induced moderate activation of p53 and dissipation of mitochondrial membrane potential. In Zn‐exposed cells, mitochondria released cytochrome c and AIF, whose translocation to the cytoplasm or the nucleus coincided with the activation of apoptosis. The use of various pharmacological inhibitors inhibiting particular apoptotic targets (antioxidants such as N‐acetyl‐cysteine and coenzyme Q, the caspase inhibitors z‐DEVD‐fmk and z‐VAD‐fmk, cyclosporin A and bonkgrekic acid) proved that Zn acts both directly and indirectly on mitochondria and observed apoptosis is executed by caspase‐dependent and caspase‐independent pathways.