Zinc induced apoptosis in HEP-2 cancer cells: the role of oxidative stress and mitochondria.
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.
Rudolf
Emil
E
Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870, Hradec Kralove I, 500 38, Czech Republic. rudolf@lfhk.cuni.cz
Rudolf
Kamil
K
Cervinka
Miroslav
M
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007822:Laryngeal Neoplasms; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010539:Permeability / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015032:Zinc / Q000378:metabolism; D019287:Zinc Sulfate / Q000494:pharmacology*
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D019287:Zinc Sulfate; D045304:Cytochromes c; D015032:Zinc