Cisplatin or LA-12 enhance killing effects of TRAIL in prostate cancer cells through Bid-dependent stimulation of mitochondrial apoptotic pathway but not caspase-10

0486057 - BFÚ 2018 RIV US eng J - Journal Article
Blanářová, Olga - Šafaříková, Barbora - Herudková, Jarmila - Krkoška, Martin - Tománková, Silvie - Kahounová, Z. - Anděra, Ladislav - Bouchal, J. - Kharaishvili, G. - Král, M. - Sova, P. - Kozubík, Alois - Vaculová, Alena
Cisplatin or LA-12 enhance killing effects of TRAIL in prostate cancer cells through Bid-dependent stimulation of mitochondrial apoptotic pathway but not caspase-10.
PLoS ONE. Roč. 12, č. 11 (2017). ISSN 1932-6203. E-ISSN 1932-6203
R&D Projects: GA ČR GA15-06650S; GA MZd(CZ) NV15-28628A
Institutional support: RVO:68081707 ; RVO:86652036
Keywords : X-LINKED INHIBITOR * PLATINUM(IV) COMPLEX LA-12 * CYTOCHROME-C
OECD category: Cell biology; Cell biology (BTO-N)
Impact factor: 2.766, year: 2017

Searching for new strategies for effective elimination of human prostate cancer cells, we investigated the cooperative cytotoxic action of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and two platinum-based complexes, cisplatin or LA-12, and related molecular mechanisms. We demonstrated a notable ability of cisplatin or LA-12 to enhance the sensitivity of several human prostate cancer cell lines to TRAIL-induced cell death via an engagement of mitochondrial apoptotic pathway. This was accompanied by augmented Bid cleavage, Bak activation, loss of mitochondrial membrane potential, activation of caspase-8, -10, -9, and -3, and XIAP cleavage. RNAi-mediated silencing of Bid or Bak in Bax-deficient DU 145 cells suppressed the drug combination-induced cytotoxicity, further underscoring the involvement of mitochondrial signaling. The caspase-10 was dispensable for enhancement of cisplatin/LA-12 and TRAIL combination-induced cell death and stimulation of Bid cleavage. Importantly, we newly demonstrated LA-12-mediated enhancement of TRAIL-induced cell death in cancer cells derived from human patient prostate tumor specimens. Our results provide convincing evidence that employing TRAIL combined with cisplatin/LA-12 could contribute to more effective killing of prostate cancer cells compared to the individual action of the drugs, and offer new mechanistic insights into their cooperative anticancer action.
Permanent Link: http://hdl.handle.net/11104/0280945