| SYSNO ASEP | 0105320
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| Druh ASEP | J - Článek v odborném periodiku
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| Zařazení RIV | J - Článek v odborném periodiku
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| Poddruh J | Ostatní články
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| Název | Alpha-tocopheryl succinate and TRAIL selectively synergise in induction of apoptosis in human malignant mesothelioma cells
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| Překlad názvu | Alfa-tokoferyl sukcinát a TRAIL selektivně spolupůsobí při vyvolání apoptózy u lidských buněk maligního mezoteliomu
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| Tvůrce(i) | Tomasetti, M. (IT)
Rippo, M. R. (IT)
Alleva, R. (IT)
Moretti, S. (IT)
Anděra, Ladislav (MBU-M)
Neuzil, J. (AU)
Procopio, A. (IT)
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| Zdroj.dok. | British Journal of Cancer. - : Springer
- ISSN 0007-0920
Roč. 90, - (2004), s. 1644-1653
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| Poč.str. | 10 s.
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| Jazyk dok. | eng - angličtina
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| Země vyd. | US - Spojené státy americké
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| Klíč. slova | TRAiL, a-TOS, apoptosis
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| Vědní obor RIV | EB - Genetika a molekulární biologie
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| CEP | LN00A026 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
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| IAA5052001 GA AV ČR - Akademie věd
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| CEZ | AV0Z5052915 - UMG-J
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| Anotace | Malignant mesothelioma (MM) is a fatal type of neoplasia with poor therapeutic prognosis, largely due to resistance to apoptosis. We investigated the apoptotic effect of a-tocopheryl succinate (a-TOS), a strong proapoptotic agent, in combination with the immunological apoptogen TNF-related apoptosis-inducing ligand (TRAIL) on both MM and nonmalignant mesothelial cells, since MM cells show low susceptibility to the clinically intriguing TRAIL. All MM cell lines tested were sensitive to a-TOS-induced apoptosis, and exerted high sensitivity to TRAIL in the presence of subapoptotic doses of the vitamin E analogue. Neither TRAIL or a-TOS alone or in combination caused apoptosis in nonmalignant mesothelial cells. Isobologram analysis of the cytotoxicity assays revealed a synergistic interaction between the two agents in MM cells and their antagonistic effect in nonmalignant mesothelial cells. TRAILinduced apoptosis and its augmentation by a-TOS were inhibited by the caspase-8 inhibitor Z-IETD-FMK and the pan-caspase inhibitor Z-VAD-FMK. Activation of caspase-8 was required to induce apoptosis, which was amplified by a-TOS via cytochrome c release following Bid cleavage, with ensuing activation of caspase-9. Enhancement of TRAIL-induced apoptosis in MM cells by a-TOS was also associated with upregulation of the TRAIL cognate death receptors DR4 and DR5. Our results show that a-TOS and TRAIL act in synergism to kill MM cells via mitochondrial pathway, and are nontoxic to nonmalignant mesothelial cells. These findings are indicative of a novel strategy for treatment of thus far fatal MM
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| Pracoviště | Ústav molekulární genetiky
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| Kontakt | Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
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| Rok sběru | 2005
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