Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) selectively induces apoptosis in transformed cells. Normal cells and certain tumor cells can evade Apo2L/TRAIL induced cell death, but the determinants of Apo2L/TRAIL sensitivity are poorly understood. To better understand the factors that contribute to Apo2L/TRAIL resistance, we characterized two colon carcinoma lines with pronounced differences in Apo2L/TRAIL sensitivity. Colo205 cells are highly sensitive to Apo2L/TRAIL whereas Colo320 cells are unresponsive. Components of the DISC (death inducing signaling complex) could be immunoprecipitated from both cell lines in response to Apo2L/TRAIL. Sensitizing agents including a proteasome inhibitor conferred Apo2L/TRAIL sensitivity in Colo320 cells, indicating that the apoptotic machinery was intact and functional. We specifically suppressed the expression of Bcl-2, FLIP or XIAP in Colo320 cells. Downregulation of either FLIP or XIAP but not Bcl-2 restored sensitivity of Colo320 cells to Apo2L/TRAIL. Moreover, stable knockdown of XIAP expression in Colo320 subcutaneous tumors resulted in suppression of tumor growth and sensitivity to Apo2L/TRAIL in vivo. Our results indicate that only a specific subset of anti-apoptotic proteins can confer resistance to Apo2L/TRAIL in Colo320 cells. Elucidation of the factors that contribute to Apo2L/TRAIL resistance in tumor cells may provide insight into combination therapies with Apo2L/TRAIL in a clinical setting.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10495-007-0076-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural and Solution Speciation Studies on -Tricarbonylrhenium(I) Complexes of 2,2'-Bipyridine Analogues.
ACS Omega
November 2024
MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7-8., H-6720 Szeged, Hungary.
Article Synopsis
- - This study explored 12 new rhenium(I) complexes, focusing on their stability and behavior in aqueous solutions, particularly how they remain intact at various pH levels without losing their ligands.
- - The complexes demonstrated varied stability in biological environments such as cell culture media and real blood serum, showing changes in solubility and lipophilicity due to ligand substitution and hydrolysis over time.
- - While the halido complexes exhibited higher cytotoxic effects against certain cancer cells compared to their aqua counterparts, both showed no antibacterial properties but some moderate antiviral activity against Herpes simplex virus 2.
Synthesis of Tumor Selective Indole and 8-Hydroxyquinoline Skeleton Containing Di-, or Triarylmethanes with Improved Cytotoxic Activity.
Molecules
September 2024
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported.
View Article and Find Full Text PDFAnalysis of naproxen activation of cell death pathways in Colo320 cells.
Mol Clin Oncol
September 2024
SCI Research Institute, Jericho, NY 11753, USA.
Colorectal cancer is a life-threatening and prevalent type of cancer. However, a number of current treatments have serious side effects, which increase the need for alternatives. Non-steroidal anti-inflammatory drugs have potential chemopreventive capabilities.
View Article and Find Full Text PDFCombination of FOLFOXIRI Drugs with Oncolytic Coxsackie B3 Virus PD-H Synergistically Induces Oncolysis in the Refractory Colorectal Cancer Cell Line Colo320.
Int J Mol Sci
May 2024
Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, 10623 Berlin, Germany.
FOLFOXIRI chemotherapy is a first-line therapy for advanced or metastatic colorectal cancer (CRC), yet its therapeutic efficacy remains limited. Immunostimulatory therapies like oncolytic viruses can complement chemotherapies by fostering the infiltration of the tumor by immune cells and enhancing drug cytotoxicity. In this study, we explored the effect of combining the FOLFOXIRI chemotherapeutic agents with the oncolytic coxsackievirus B3 (CVB3) PD-H in the CRC cell line Colo320.
View Article and Find Full Text PDFFast Track Adaptation of Oncolytic Coxsackie B3 Virus to Resistant Colorectal Cancer Cells - a Method to Personalize Virotherapy.
Biol Proced Online
April 2024
Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Straße des 17. Juni 135, 10623, Berlin, Germany.
Background: The efficacy of oncolytic viruses (OV) in cancer treatment depends on their ability to successfully infect and destroy tumor cells. However, patients' tumors vary, and in the case of individual insensitivity to an OV, therapeutic efficacy is limited. Here, we present a protocol for rapid generation of tumor cell-specific adapted oncolytic coxsackievirus B3 (CVB3) with enhanced oncolytic potential and a satisfactory safety profile.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!