Abstract
Some fatty acids and derivatives are known to induce cell death in cancer cells. Mitochondria may have important roles in the death process. Therefore, we investigated the mitochondrial contribution in cell death induced by a modified fatty acid, tetradecylthioacetic acid (TTA), which cannot be beta-oxidized. TTA treatment induced apoptosis in IPC-81 leukemia cells via depolarization of the mitochondrial membrane potential (deltapsi) and early release of cytochrome c, accompanied by depletion of mitochondrial glutathione. Caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP) occurred at a late stage, but the broad-spectra caspase inhibitor zVAD-fmk did not block TTA-induced apoptosis. Overexpression of Bcl-2 partially prevented TTA-induced apoptosis, whereas cAMP-induced cell death was completely blocked. In conclusion, TTA seems to trigger apoptosis through mitochondrial-mediated mechanisms and selective modulation of the mitochondrial redox equilibrium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Blotting, Western
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Caspases / metabolism
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Cell Line, Tumor
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Cell Nucleus / drug effects
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Cell Nucleus / ultrastructure
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Cyclic AMP / analogs & derivatives*
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Cyclic AMP / pharmacology
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Cytochromes c / metabolism
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Cytosol / drug effects
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Cytosol / metabolism
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Fluorescent Dyes
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Gene Expression Regulation, Neoplastic / drug effects
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Genes, bcl-2 / genetics
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Glutathione / metabolism*
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Image Processing, Computer-Assisted
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Immunoassay
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Leukemia, Promyelocytic, Acute / metabolism*
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Mice
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Mitochondria / drug effects*
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Mitochondria / metabolism
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Mitochondria / ultrastructure
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Subcellular Fractions / drug effects
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Subcellular Fractions / metabolism
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Sulfides / pharmacology*
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Thionucleotides / pharmacology
Substances
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Antineoplastic Agents
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Fluorescent Dyes
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Sulfides
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Thionucleotides
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8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
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1-(carboxymethylthio)tetradecane
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Cytochromes c
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Cyclic AMP
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Caspases
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Glutathione