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001-es BibID:BIBFORM020773
Első szerző:Vondalova, Blanarova O.
Cím:Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway / Vondalova, B. O., Jelinkova, I., Szoor, A., Skender, B., Soucek, K., Horvath, V., Vaculova, A., Andera, L., Sova, P., Szollosi, J., Hofmanova, J., Vereb, G., Kozubik, A.
Dátum:2011
Megjegyzések:TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
ACTIVATION
Amantadine
analogs & derivatives
Apoptosis
article
Biophysics
Blotting,Western
Cell Line
Cell Line,Tumor
Cell Separation
Cells
Cisplatin
drug effects
Flow Cytometry
Fluorescent Antibody Technique
Human
Humans
ligand
lipid raft
LIPID RAFTS
metabolism
Microscopy,Confocal
Necrosis
Neoplasms
Organoplatinum Compounds
pharmacology
physiology
Protein Transport
Receptors,TNF-Related Apoptosis-Inducing Ligand
Research
Research Support
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Signal Transduction
Support
therapy
TNF-Related Apoptosis-Inducing Ligand
Megjelenés:Carcinogenesis. - 32 : 1 (2011), p. 42-51. -
További szerzők:Jelínková, Iva Szöőr Árpád (1984-) (orvos) Skender, Belma Soucek, Karel Horváth Viktor Vaculova, Alena Andera, Ladislav Sova, Petr Szöllősi János (1953-) (biofizikus) Hofmanova, Jirin Vereb György (1965-) (biofizikus, orvos) Kozubik, Alois
Internet cím:DOI
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