Mechanism of α-tocopheryl succinate-induced apoptosis of promyelocytic leukemia cells
| Autor: | Rumi Ishisaka, Hirotsugu Kobuchi, Kayo Arita, Tomoko Kanno, Kozo Utsumi, Hiroshi Tamai, Shinji Yamamoto |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Tocopherols Apoptosis DNA Fragmentation Cysteine Proteinase Inhibitors Mitochondrion medicine.disease_cause Biochemistry Calcium in biology Amino Acid Chloromethyl Ketones Leukemia Promyelocytic Acute Tumor Cells Cultured medicine Animals Humans Vitamin E Rats Wistar Caspase biology DNA synthesis Cytochrome c Cell Differentiation DNA General Medicine Caspase Inhibitors Mitochondria Rats Cell biology Enzyme Activation Cytosol Caspases biology.protein biological phenomena cell phenomena and immunity Reactive Oxygen Species Cell Division Oxidative stress |
| Zdroj: | Free Radical Research. 33:407-418 |
| ISSN: | 1029-2470 1071-5762 |
| DOI: | 10.1080/10715760000300941 |
| Popis: | Selective induction of apoptosis in tumor cells is important for treating patients with cancer. Because oxidative stress plays an important role in the process of apoptosis, we studied the effect of alpha-tocopheryl succinate (VES) on the fate of cultured human promyelocytic leukemia cells (HL-60). The presence of fairly low concentrations of VES inhibited the growth and DNA synthesis of HL-60 cells, and also induced their apoptosis via a mechanism that was inhibited by z-VAD-fluoromethylketone (z-VAD-fmk), an inhibitor of pan-caspases. VES activated various types of caspases, including caspase-3, 6, 8, and 9, but not caspase-1. VES triggered the reaction leading to the cleavage of Bid, a member of the death agonist Bcl-2 family, and released cytochrome c (Cyt.c) from the mitochondria into the cytosol by a z-VAD-fmk-inhibitable mechanism. VES transiently increased the intracellular calcium level [Ca2+]i and stimulated the release of Cyt.c in the presence of inorganic phosphate (Pi). However, high concentrations of VES (approximately 100 microM) hardly induced swelling of isolated mitochondria but depolarized the mitochondrial membrane potential by a cyclosporin A (CsA)-insensitive mechanism. These results indicate that VES-induced apoptosis of HL-60 cells might be caused by activation of the caspase cascade coupled with modulation of mitochondrial membrane function. |
| Databáze: | OpenAIRE |
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