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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F14%3A00107101" target="_blank" >RIV/00216224:14310/14:00107101 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/14:00440152 RIV/00159816:_____/14:00061244 RIV/61989592:15110/14:33149998

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0006295214005577" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0006295214005577</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bcp.2014.09.013" target="_blank" >10.1016/j.bcp.2014.09.013</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2014

Confidentiality

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

Name of the periodical

Biochemical Pharmacology

ISSN

0006-2952

e-ISSN

1873-2968

Volume of the periodical

92

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

415-424

UT code for WoS article

000345955400002

EID of the result in the Scopus database

2-s2.0-84910612051