Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells
- 11 May 2006
- journal article
- Published by Springer Nature in Apoptosis
- Vol. 11 (7) , 1239-1246
- https://doi.org/10.1007/s10495-006-7494-8
Abstract
Combined treatment modalities using tumor necrosis factor related apoptosis-inducing ligand L (TRAIL) and cytotoxic drugs revealed highly additive effects in some tumor cell lines. Little is known about the efficacy and underlying mechanistic effects of the modalities in chemoresistant tumor cells. The purpose of this study is to investigate the possible role of JNK in the synergistic effect in Doxorubicin (Adriamycin, ADM) resistant MCF-7/ADM cells. Here we showed that the JNK pathway was activated slightly by TRAIL in MCF-7/ADM cell lines and was enhanced by the combination of the two treatments. Inhibition of JNK activity by transfection with dominant-negative JNK blocks TRAIL plus ADM induced-apoptosis significantly, and selective stimulation of the JNK pathway sensitizes ADM resistant breast cancer cells to ADM and TRAIL co-treatment through activation of mitochondria-regulated apoptotic pathway. We conclude that the JNK pathway plays an important role in mediating TRAIL plus ADM induced-apoptosis in breast cancer cells.Keywords
This publication has 23 references indexed in Scilit:
- Sustained Activation of JNK/p38 MAPK Pathways in Response to Cisplatin Leads to Fas Ligand Induction and Cell Death in Ovarian Carcinoma CellsJournal of Biological Chemistry, 2003
- Long-term tumor-free survival from treatment with the GFP–TRAIL fusion gene expressed from the hTERT promoter in breast cancer cellsOncogene, 2002
- Signal Transduction by the JNK Group of MAP KinasesPublished by Elsevier ,2000
- Doxorubicin Treatment Activates a Z-VAD-Sensitive Caspase, Which Causes ΔΨm Loss, Caspase-9 Activity, and Apoptosis in Jurkat CellsExperimental Cell Research, 2000
- Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death PathwayScience, 2000
- Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptors Signal NF-κB and JNK Activation and Apoptosis through Distinct PathwaysJournal of Biological Chemistry, 1999
- Caspases: Enemies WithinScience, 1998
- Upregulation of cytokeratins 8 and 18 in human breast cancer T47D cells is retinoid-specific and retinoic acid receptor-dependentDifferentiation, 1996
- Identification and characterization of a new member of the TNF family that induces apoptosisImmunity, 1995
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993