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
| Autor: | Ladislav Anděra, Alena Hyršlová Vaculová, Silvie Tománková, Jan Bouchal, Milan Král, Martin Krkoška, Petr Sova, Zuzana Kahounová, Barbora Šafaříková, Gvantsa Kharaishvili, Alois Kozubík, Olga Vondálová Blanářová, Jarmila Herůdková |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Male Organoplatinum Compounds Cancer Treatment lcsh:Medicine Apoptosis Synthetic Biotechnology Mitochondrion Biochemistry TNF-Related Apoptosis-Inducing Ligand Prostate cancer 0302 clinical medicine Spectrum Analysis Techniques Medicine and Health Sciences Cytotoxic T cell lcsh:Science Caspase 10 Energy-Producing Organelles Multidisciplinary Cell Death Pharmaceutics Prostate Cancer Prostate Diseases Flow Cytometry Cell biology XIAP Mitochondria Chemistry Oncology Cell Processes Spectrophotometry 030220 oncology & carcinogenesis Physical Sciences Engineering and Technology Synthetic Biology Cytophotometry Cellular Structures and Organelles medicine.drug Research Article Chemical Elements Biotechnology BH3 Interacting Domain Death Agonist Protein Programmed cell death Urology Biology Bioenergetics Research and Analysis Methods 03 medical and health sciences Drug Therapy medicine Amantadine Humans Synthetic Peptides Platinum Cisplatin lcsh:R Biology and Life Sciences Cancers and Neoplasms Prostatic Neoplasms Cell Biology medicine.disease Genitourinary Tract Tumors 030104 developmental biology Cancer cell lcsh:Q Peptides |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 11, p e0188584 (2017) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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