Alfa-tokoferyl sukcinát potlačuje maligní mezoteliom přerušením autokrinní smyčky fibroblastového růstového faktoru

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F05%3A00001318" target="_blank" >RIV/68378050:_____/05:00001318 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop

Popis výsledku v původním jazyce

We studied the potential effect against human malignant mesotheliomas (MM) of alpha-tocopheryl succinate (alpha-TOS), a redox-silent vitamin E analog with strong pro-apoptotic and anti-cancer activity. alpha-TOS at sub-apoptotic levels inhibited proliferation of MM cell lines, while being nontoxic to nonmalignant mesothelial cells. Because MM cells are typified by a highly metastatic phenotype, we investigated the effect of alpha-TOS on genes playing a major role in MM progression. Of these, alpha-TOS downregulated fibroblast growth factor (FGF)-1 and, in particular, FGF-2 on the transcriptional level in MM cells, and this was not observed in their nonmalignant counterparts. alpha-TOS significantly suppressed experimental MM in immunocompromised mice.Our data suggest that alpha-TOS suppresses MM cell proliferation by disrupting the FGF-FGF receptor autocrine signaling loop by generating oxidative stress and point to the agent as a selective drug against thus far fatal mesotheliomas.

Název v anglickém jazyce

Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop

Popis výsledku anglicky

We studied the potential effect against human malignant mesotheliomas (MM) of alpha-tocopheryl succinate (alpha-TOS), a redox-silent vitamin E analog with strong pro-apoptotic and anti-cancer activity. alpha-TOS at sub-apoptotic levels inhibited proliferation of MM cell lines, while being nontoxic to nonmalignant mesothelial cells. Because MM cells are typified by a highly metastatic phenotype, we investigated the effect of alpha-TOS on genes playing a major role in MM progression. Of these, alpha-TOS downregulated fibroblast growth factor (FGF)-1 and, in particular, FGF-2 on the transcriptional level in MM cells, and this was not observed in their nonmalignant counterparts. alpha-TOS significantly suppressed experimental MM in immunocompromised mice.Our data suggest that alpha-TOS suppresses MM cell proliferation by disrupting the FGF-FGF receptor autocrine signaling loop by generating oxidative stress and point to the agent as a selective drug against thus far fatal mesotheliomas.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

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Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2005

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Svazek periodika

280

Číslo periodika v rámci svazku

27

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

25369-25376

Kód UT WoS článku

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EID výsledku v databázi Scopus

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