• Something wrong with this record ?

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

J. Molinsky, M. Klanova, M. Koc, L. Beranova, L. Andera, Z. Ludvikova, M. Bohmova, Z. Gasova, M. Strnad, R. Ivanek, M. Trneny, E. Necas, J. Zivny, P. Klener,

. 2013 ; 54 (2) : 372-80.

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc13024373

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 mitochondrial priming and enhanced processing of apical caspases represent major molecular mechanisms of roscovitine-induced sensitization to TRAIL in leukemia/lymphoma cells.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc13024373
003      
CZ-PrNML
005      
20130710110446.0
007      
ta
008      
130703s2013 enk f 000 0|eng||
009      
AR
024    7_
$a 10.3109/10428194.2012.710331 $2 doi
035    __
$a (PubMed)22830613
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Molinsky, Jan $u Institute of Pathological Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
245    10
$a Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis / $c J. Molinsky, M. Klanova, M. Koc, L. Beranova, L. Andera, Z. Ludvikova, M. Bohmova, Z. Gasova, M. Strnad, R. Ivanek, M. Trneny, E. Necas, J. Zivny, P. Klener,
520    9_
$a 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 mitochondrial priming and enhanced processing of apical caspases represent major molecular mechanisms of roscovitine-induced sensitization to TRAIL in leukemia/lymphoma cells.
650    _2
$a zvířata $7 D000818
650    _2
$a protinádorové látky $x farmakologie $7 D000970
650    _2
$a apoptóza $x účinky léků $7 D017209
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a cytotoxicita imunologická $x účinky léků $7 D003602
650    _2
$a signální adaptorové proteiny receptorové domény smrti $x metabolismus $7 D053418
650    _2
$a ligand Fas $x farmakologie $7 D053222
650    _2
$a lidé $7 D006801
650    _2
$a leukemie $x genetika $x metabolismus $x patologie $7 D007938
650    _2
$a lymfom $x genetika $x metabolismus $x patologie $7 D008223
650    _2
$a myši $7 D051379
650    _2
$a mitochondrie $x účinky léků $x metabolismus $7 D008928
650    _2
$a proteosyntéza $x účinky léků $7 D014176
650    _2
$a protoonkogenní proteiny c-bcl-2 $x metabolismus $7 D019253
650    _2
$a puriny $x farmakologie $7 D011687
650    _2
$a protein TRAIL $x farmakologie $7 D053221
650    _2
$a genetická transkripce $x účinky léků $7 D014158
650    _2
$a tumor burden $x účinky léků $7 D047368
650    _2
$a TNF-alfa $x farmakologie $7 D014409
650    _2
$a xenogenní modely - testy protinádorové aktivity $7 D023041
650    _2
$a protein bcl-X $x metabolismus $7 D051020
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Klanova, Magdalena $u -
700    1_
$a Koc, Michal $u -
700    1_
$a Beranova, Lenka $u -
700    1_
$a Andera, Ladislav $u - $7 gn_A_00006005
700    1_
$a Ludvikova, Zdenka $u -
700    1_
$a Bohmova, Martina $u -
700    1_
$a Gasova, Zdenka $u -
700    1_
$a Strnad, Miroslav $u -
700    1_
$a Ivanek, Robert $u -
700    1_
$a Trneny, Marek $u -
700    1_
$a Necas, Emanuel $u -
700    1_
$a Zivny, Jan $u -
700    1_
$a Klener, Pavel $u -
773    0_
$w MED00003140 $t Leukemia & lymphoma $x 1029-2403 $g Roč. 54, č. 2 (2013), s. 372-80
856    41
$u https://pubmed.ncbi.nlm.nih.gov/22830613 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20130703 $b ABA008
991    __
$a 20130710110909 $b ABA008
999    __
$a ok $b bmc $g 988053 $s 822753
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2013 $b 54 $c 2 $d 372-80 $i 1029-2403 $m Leukemia & lymphoma $n Leuk Lymphoma $x MED00003140
LZP    __
$a Pubmed-20130703

Find record

Citation metrics

Archiving options