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@article{1593022,
author = {Jelínková, Iva and Šafaříková, Barbora and Blanarova, Olga Vondalova and Skender, Belma and Hofmanová, Jiřina and Sova, Petr and Moyer, Mary Pat and Kozubík, Alois and Kolar, Zdenek and Ehrmann, Jiri and Vaculova, Alena Hyrslova},
article_location = {OXFORD},
article_number = {3},
doi = {http://dx.doi.org/10.1016/j.bcp.2014.09.013},
keywords = {TRAIL; LA-12; Cisplatin; Apoptosis; Colon cancer},
language = {eng},
issn = {0006-2952},
journal = {Biochemical Pharmacology},
title = {Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway},
url = {https://www.sciencedirect.com/science/article/pii/S0006295214005577},
volume = {92},
year = {2014}
}
TY - JOUR
ID - 1593022
AU - Jelínková, Iva - Šafaříková, Barbora - Blanarova, Olga Vondalova - Skender, Belma - Hofmanová, Jiřina - Sova, Petr - Moyer, Mary Pat - Kozubík, Alois - Kolar, Zdenek - Ehrmann, Jiri - Vaculova, Alena Hyrslova
PY - 2014
TI - Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway
JF - Biochemical Pharmacology
VL - 92
IS - 3
SP - 415-424
EP - 415-424
PB - PERGAMON-ELSEVIER SCIENCE LTD
SN - 00062952
KW - TRAIL
KW - LA-12
KW - Cisplatin
KW - Apoptosis
KW - Colon cancer
UR - https://www.sciencedirect.com/science/article/pii/S0006295214005577
L2 - https://www.sciencedirect.com/science/article/pii/S0006295214005577
N2 - 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. We newly demonstrated that LA-12 induced ERIC-mediated c-Myc upregulation, and proved that c-Myc silencing inhibited the mitochondrial activation and apoptosis in colon cancer cells treated with LA-12 and TRAIL The LA-12-mediated sensitization to TRAIL-induced apoptosis was demonstrated in several colon cancer cell lines, further underscoring the general relevance of our findings. The selective action of LA-12 was documented by preferential priming of cancer but not normal colon cancer cells to TRAIL killing effects. Our work highlights the promising potential of LA-12 over cisplatin to enhance the colon cancer cell sensitivity to TRAIL-induced apoptosis, and provides new mechanistic insights into their cooperative action.
ER -
JELÍNKOVÁ, Iva, Barbora ŠAFAŘÍKOVÁ, Olga Vondalova BLANAROVA, Belma SKENDER, Jiřina HOFMANOVÁ, Petr SOVA, Mary Pat MOYER, Alois KOZUBÍK, Zdenek KOLAR, Jiri EHRMANN and Alena Hyrslova VACULOVA. Platinum(IV) complex LA-12 exerts higher ability than cisplatin to enhance TRAIL-induced cancer cell apoptosis via stimulation of mitochondrial pathway. \textit{Biochemical Pharmacology}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2014, vol.~92, No~3, p.~415-424. ISSN~0006-2952. Available from: https://dx.doi.org/10.1016/j.bcp.2014.09.013.
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