About: Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway     Goto   Sponge   Distinct   Permalink

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  • In search for novel strategies in colon cancer treatment, we investigated the unique ability of platinum(IV) complex LA-12 to efficiently enhance the killing effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and compared it with the sensitizing action of cisplatin. We provide the first evidence that LA-12 primes human colon cancer cells for TRAIL-induced cytotoxicity by p53-independent activation of the mitochondrial apoptotic pathway. The cooperative action of LA-12 and TRAIL was associated with stimulation of Bax/Bak activation, drop of mitochondrial membrane potential, caspase-9 activation, and a shift of the balance among BcI-2 family proteins in favor of the proapoptotic members. In contrast to cisplatin, LA-12 was a potent inducer of ERIC-mediated Noxa and Birn(L) protein upregulation, and more effectively enhanced TRAIL-induced apoptosis in the absence of Bax. The cooperative action of LA-12 and TRAIL was augmented following the siRNA-mediated silencing of Mcl-1 in both Bax proficient/deficient cells.
  • In search for novel strategies in colon cancer treatment, we investigated the unique ability of platinum(IV) complex LA-12 to efficiently enhance the killing effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and compared it with the sensitizing action of cisplatin. We provide the first evidence that LA-12 primes human colon cancer cells for TRAIL-induced cytotoxicity by p53-independent activation of the mitochondrial apoptotic pathway. The cooperative action of LA-12 and TRAIL was associated with stimulation of Bax/Bak activation, drop of mitochondrial membrane potential, caspase-9 activation, and a shift of the balance among BcI-2 family proteins in favor of the proapoptotic members. In contrast to cisplatin, LA-12 was a potent inducer of ERIC-mediated Noxa and Birn(L) protein upregulation, and more effectively enhanced TRAIL-induced apoptosis in the absence of Bax. The cooperative action of LA-12 and TRAIL was augmented following the siRNA-mediated silencing of Mcl-1 in both Bax proficient/deficient cells. (en)
Title
  • Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway
  • Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway (en)
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  • Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway
  • Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway (en)
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  • RIV/68081707:_____/14:00440152!RIV15-AV0-68081707
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  • I, P(ED1.100/02/0123)
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  • 3
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  • 36844
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  • RIV/68081707:_____/14:00440152
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  • IN-VITRO; C-MYC; CHEMOTHERAPEUTIC DRUGS (en)
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  • US - Spojené státy americké
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  • Biochemical Pharmacology
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  • 92
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  • Hofmanová, Jiřina
  • Jelínková, Iva
  • Kozubík, Alois
  • Skender, Belma
  • Vaculová, Alena
  • Ehrmann, J.
  • Kolář, Z.
  • Blanářová, Olga
  • Sova, P.
  • Moyer, M. P.
  • Šafaříková, Barbora
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  • 000345955400002
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  • 0006-2952
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  • 10.1016/j.bcp.2014.09.013
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