Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F13%3A00011512" target="_blank" >RIV/00064165:_____/13:00011512 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/13:00398210 RIV/68378050:_____/13:00398210 RIV/61989592:15310/13:33142821 RIV/00216208:11110/13:00011512 RIV/00023736:_____/13:00010655

Výsledek na webu

<a href="http://dx.doi.org/10.3109/10428194.2012.710331" target="_blank" >http://dx.doi.org/10.3109/10428194.2012.710331</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3109/10428194.2012.710331" target="_blank" >10.3109/10428194.2012.710331</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

Popis výsledku v původním jazyce

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. We show that roscovitine and TRAIL demonstrate synergistic cytotoxicity in hematologic malignant cell lines and primary cells. Pretreatment of TRAIL-resistant leukemia cells with roscovitine induced enhanced cleavage of death-inducing signaling complex-bound proximal caspases after exposure to TRAIL. We observed increased levels of both pro- and antiapoptotic BCL-2 proteins at the mitochondria following exposure to roscovitine. These results suggest that roscovitine induces priming of cancer cells for death by binding antiapoptotic BCL-2 proteins to proapoptotic BH3-only proteins at the mitochondria, thereby decreasing the threshold for diverse proapoptotic stimuli. We propose that the mitochond

Název v anglickém jazyce

Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

Popis výsledku anglicky

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. We show that roscovitine and TRAIL demonstrate synergistic cytotoxicity in hematologic malignant cell lines and primary cells. Pretreatment of TRAIL-resistant leukemia cells with roscovitine induced enhanced cleavage of death-inducing signaling complex-bound proximal caspases after exposure to TRAIL. We observed increased levels of both pro- and antiapoptotic BCL-2 proteins at the mitochondria following exposure to roscovitine. These results suggest that roscovitine induces priming of cancer cells for death by binding antiapoptotic BCL-2 proteins to proapoptotic BH3-only proteins at the mitochondria, thereby decreasing the threshold for diverse proapoptotic stimuli. We propose that the mitochond

Druh

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

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Leukemia and Lymphoma

ISSN

1042-8194

e-ISSN

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Svazek periodika

54

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

372-380

Kód UT WoS článku

000313285400027

EID výsledku v databázi Scopus

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